U.S. patent application number 10/120907 was filed with the patent office on 2004-04-01 for nucleic acid and corresponding protein entitled 151p3d4 useful in treatment and detection of cancer.
Invention is credited to Challita-Eid, Pia M., Faris, Mary, Ge, Wangmao, Hubert, Rene S., Jakobovits, Aya, Morrison, Karen Jane Meyrick, Morrison, Robert Kendall, Raitano, Arthur B..
Application Number | 20040062761 10/120907 |
Document ID | / |
Family ID | 26961649 |
Filed Date | 2004-04-01 |
United States Patent
Application |
20040062761 |
Kind Code |
A1 |
Challita-Eid, Pia M. ; et
al. |
April 1, 2004 |
Nucleic acid and corresponding protein entitled 151P3D4 useful in
treatment and detection of cancer
Abstract
A novel gene (designated 151P3D4) and its encoded protein, and
variants thereof, are described wherein 151P3D4 exhibits tissue
specific expression in normal adult tissue, and is aberrantly
expressed in the cancers listed in Table I. Consequently, 151P3D4
provides a diagnostic, prognostic, prophylactic and/or therapeutic
target for cancer. The 151P3D4 gene or fragment thereof, or its
encoded protein, or variants thereof, or a fragment thereof, can be
used to elicit a humoral or cellular immune response; antibodies or
T cells reactive with 151P3D4 can be used in active or passive
immunization.
Inventors: |
Challita-Eid, Pia M.;
(Encino, CA) ; Raitano, Arthur B.; (Los Angeles,
CA) ; Faris, Mary; (Los Angeles, CA) ; Hubert,
Rene S.; (Los Angeles, CA) ; Morrison, Karen Jane
Meyrick; (Santa Monica, CA) ; Morrison, Robert
Kendall; (Santa Monica, CA) ; Ge, Wangmao;
(Culver City, CA) ; Jakobovits, Aya; (Beverly
Hills, CA) |
Correspondence
Address: |
Kate H. Murashige
Morrison & Foerster LLP
Suite 500
3811 Valley Centre Drive
San Diego
CA
92130-2332
US
|
Family ID: |
26961649 |
Appl. No.: |
10/120907 |
Filed: |
April 9, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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60286630 |
Apr 25, 2001 |
|
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60282739 |
Apr 10, 2001 |
|
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Current U.S.
Class: |
424/130.1 ;
435/326; 530/350; 530/387.1; 800/8 |
Current CPC
Class: |
C07K 14/47 20130101;
C12N 9/78 20130101; A61K 38/00 20130101; Y10T 436/25 20150115; A61P
35/00 20180101; A61P 31/00 20180101 |
Class at
Publication: |
424/130.1 ;
530/387.1; 435/326; 530/350; 800/008 |
International
Class: |
A01K 067/00; A61K
039/395; C12N 005/06; C07K 014/47 |
Claims
1. A composition comprising: a substance that a) modulates the
status of a protein of FIG. 2 (SEQ ID NOS:______), or b) a molecule
that is modulated by a protein of FIG. 2, whereby the status of a
cell that expresses a protein of FIG. 2 is modulated.
2. A composition of claim 1, further comprising a physiologically
acceptable carrier.
3. A pharmaceutical composition that comprises the composition of
claim 1 in a human unit dose form.
4. A composition of claim 1 wherein the substance comprises an
antibody or fragment thereof that specifically binds to a protein
that is related to a protein of FIG. 2.
5. An antibody or fragment thereof of claim 4, which is
monoclonal.
6. An antibody of claim 4, which is a human antibody, a humanized
antibody or a chimeric antibody.
7. A non-human transgenic animal that produces an antibody of claim
4.
8. A hybridoma that produces an antibody of claim 5.
9. A method of delivering a cytotoxic agent or a diagnostic agent
to a cell that expresses a protein of FIG. 2 (SEQ ID NOS: ______),
said method comprising: providing the cytotoxic agent or the
diagnostic agent conjugated to an antibody or fragment thereof of
claim 4; and, exposing the cell to the antibody-agent or
fragment-agent conjugate.
10. A composition of claim 1 wherein the substance comprises a
polynucleotide that encodes an antibody or fragment thereof, either
of which immunospecifically bind to a protein of FIG. 2.
11. A composition of claim 1 wherein the substance comprises a
protein related to a protein of FIG. 2.
12. A protein of claim 11 that is at least 90% homologous to an
entire amino acid sequence shown in FIG. 2 (SEQ ID NOS:
______).
13. A composition of claim 1 wherein the substance comprises: a) a
peptide of eight, nine, ten, or eleven contiguous amino acids of a
protein of FIG. 2; b) a peptide of Tables V to XVIII (SEQ ID NOS:
______); c) a peptide of Tables XXII to XLVII (SEQ ID NOS: ______);
or, d) a peptide of Tables XLVIII to LI (SEQ ID NOS: ______).
14. A composition of claim 1 wherein the substance comprises a CTL
polypeptide or an analog thereof, from the amino acid sequence of a
protein of FIG. 2 (SEQ ID NOS: ______).
15. A composition of claim 14 further limited by a proviso that the
epitope is not an entire amino acid sequence of FIG. 2 (SEQ ID
NOS:).
16. A composition of claim 14 wherein the substance comprises a CTL
polypeptide set forth in Tables V to XVIII (SEQ ID NOS:
______).
17. A composition of claim 16 further limited by a proviso that the
polypeptide is not an entire amino acid sequence of a protein of
FIG. 2 (SEQ ID NOS: ______).
18. A composition of claim 1 wherein the substance comprises an
antibody polypeptide epitope from an amino acid sequence of FIG. 2
(SEQ ID NOS: ______).
19. A composition of claim 18 further limited by a proviso that the
epitope is not an entire amino acid sequence of FIG. 2 (SEQ ID NOS:
______).
20. A composition of claim 18 wherein the antibody epitope
comprises a peptide region of at least 5 amino acids of FIG. 2 (SEQ
ID NOS: ______) in any whole number increment up to the end of said
peptide, wherein the epitope comprises an amino acid position
selected from: a) an amino acid position having a value greater
than 0.5 in the Hydrophilicity profile of FIG. 5, b) an amino acid
position having a value less than 0.5 in the Hydropathicity profile
of FIG. 6; c) an amino acid position having a value greater than
0.5 in the Percent Accessible Residues profile of FIG. 7; d) an
amino acid position having a value greater than 0.5 in the Average
Flexibility profile of FIG. 8; e) an amino acid position having a
value greater than 0.5 in the Beta-turn profile of FIG. 9; f) a
combination of at least two of a) through e); g) a combination of
at least three of a) through e); h) a combination of at least four
of a) through e); or i) a combination of five of a) through e).
21. A composition of claim 20 further limited by a proviso that the
epitope is not an entire amino acid sequence of FIG. 2 (SEQ ID NOS:
______).
22. A polynucleotide that encodes a protein of claim 11.
23. A polynucleotide of claim 22 that comprises a nucleic acid
molecule set forth in FIG. 2.
24. A polynucleotide of claim 22 further limited by a proviso that
the encoded protein is not an entire amino acid sequence of FIG. 2
(SEQ ID NOS: ______).
25. A polynucleotide of claim 22 wherein T is substituted with
U.
26. A composition of claim 1 wherein the substance comprises a
polynucleotide that comprises a coding sequence of a nucleic acid
sequence of FIG. 2 (SEQ ID NOS: ______).
27. A polynucleotide of claim 22 that further comprises an
additional nucleotide sequence that encodes an additional protein
of claim 11.
28. A composition comprising a polynucleotide that is fully
complementary to a polynucleotide of claim 22.
29. A composition comprising a polynucleotide that is fully
complementary to a polynucleotide of claim 25.
30. A composition comprising a polynucleotide that is fully
complementary to a polynucleotide of claim 27.
31. A composition of claim 1 wherein the substance comprises a) a
ribozyme that cleaves a polynucleotide having a 151P3D4 coding
sequence, or b) a nucleic acid molecule that encodes the ribozyme;
and, a physiologically acceptable carrier.
32. A composition of claim 1 wherein the substance comprises human
T cells, wherein said T cells specifically recognize a 151P3D4
peptide subsequence in the context of a particular HLA
molecule.
33. A method of inhibiting growth of cancer cells that express a
protein of FIG. 2, the method comprising: administering to the
cells the composition of claim 1.
34. A method of claim 33 of inhibiting growth of cancer cells that
express a protein of FIG. 2, the method comprising steps of:
administering to said cells an antibody or fragment thereof, either
of which specifically bind to a 151P3D4-related protein.
35. A method of claim 33 of inhibiting growth of cancer cells that
express a protein of FIG. 2, the method comprising steps of:
administering to said cells a 151P3D4-related protein.
36. A method of claim 33 of inhibiting growth of cancer cells that
express a protein of FIG. 2, the method comprising steps of:
administering to said cells a polynucleotide comprising a coding
sequence for a 151P3D4-related protein or comprising a
polynucleotide complementary to a coding sequence for a
151P3D4-related protein.
37. A method of claim 33 of inhibiting growth of cancer cells that
express a protein of FIG. 2, the method comprising steps of:
administering to said cells a ribozyme that cleaves a
polynucleotide that encodes a protein of FIG. 2.
38. A method of claim 33 of inhibiting growth of cancer cells that
express a protein of FIG. 2 and a particular HLA molecule, the
method comprising steps of: administering human T cells to said
cancer cells, wherein said T cells specifically recognize a peptide
subsequence of a protein of FIG. 2 while the subsequence is in the
context of the particular HLA molecule.
39. A method of claim 33, the method comprising steps of:
administering a vector that delivers a nucleotide that encodes a
single chain monoclonal antibody, whereby the encoded single chain
antibody is expressed intracellularly within cancer cells that
express a protein of FIG. 2.
40. A method of generating a mammalian immune response directed to
a protein of FIG. 2, the method comprising: exposing cells of the
mammal's immune system to a portion of a) a 151P3D4-related protein
and/or b) a nucleotide sequence that encodes said protein, whereby
an immune response is generated to said protein.
41. A method of generating an immune response of claim 40, said
method comprising: providing a 151P3D4-related protein that
comprises at least one T cell or at least one B cell epitope; and,
contacting the epitope with a mammalian immune system T cell or B
cell respectively, whereby the T cell or B cell is activated.
42. A method of claim 41 wherein the immune system cell is a B
cell, whereby the induced B cell generates antibodies that
specifically bind to the 151P3D4-related protein.
43. A method of claim 41 wherein the immune system cell is a T cell
that is a cytotoxic T cell (CTL), whereby the activated CTL kills
an autologous cell that expresses the 151P3D4-related protein.
44. A method of claim 41 wherein the immune system cell is a T cell
that is a helper T cell (HTL), whereby the activated HTL secretes
cytokines that facilitate the cytotoxic activity of a cytotoxic T
cell (CTL) or the antibody-producing activity of a B cell.
45. A method for detecting, in a sample, the presence of a
151P3D4-related protein or a 151P3D4-related polynucleotide,
comprising steps of: contacting the sample with a substance of
claim 1 that specifically binds to the 151P3D4-related protein or
to the 151P3D4-related polynucleotide, respectively; and,
determining that there is a complex of the substance with the
151P3D4-related protein or the substance with the 151P3D4-related
polynucleotide, respectively.
46. A method of claim 45 for detecting the presence of a
151P3D4-related protein in a sample comprising steps of: contacting
the sample with an antibody or fragment thereof either of which
specifically bind to the 151P3D4-related protein; and, determining
that there is a complex of the antibody or fragment thereof and the
151P3D4-related protein.
47. A method of claim 45 further comprising a step of: taking the
sample from a patient who has or who is suspected of having
cancer.
48. A method of claim 45 for detecting the presence of a protein of
FIG. 2 mRNA in a sample comprising: producing cDNA from the sample
by reverse transcription using at least one primer; amplifying the
cDNA so produced using 151P3D4 polynucleotides as sense and
antisense primers, wherein the 151P3D4 polynucleotides used as the
sense and antisense primers serve to amplify a 151P3D4 cDNA; and,
detecting the presence of the amplified 151P3D4 cDNA.
49. A method of claim 45 for monitoring one or more 151P3D4 gene
products in a biological sample from a patient who has or who is
suspected of having cancer, the method comprising: determining the
status of one or more 151P3D4 gene products expressed by cells in a
tissue sample from an individual; comparing the status so
determined to the status of one or more 151P3D4 gene products in a
corresponding normal sample; and, identifying the presence of one
or more aberrant gene products of 151P3D4 in the sample relative to
the normal sample.
50. The method of claim 49 further comprising a step of determining
if there are one or more elevated gene products of a 151P3D4 mRNA
or a 151P3D4 protein, whereby the presence of one or more elevated
gene products in the test sample relative to the normal tissue
sample indicates the presence or status of a cancer.
51. A method of claim 50 wherein the cancer occurs in a tissue set
forth in Table I.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority from U.S. Serial No.
60/282,739 filed Apr. 10, 2001, and U.S. Serial No. 60/286,630,
filed Apr. 25, 2001. The contents of these applications are hereby
incorporated by reference herein in their entirety.
STATEMENT OF RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED
RESEARCH
[0002] Not applicable.
FIELD OF THE INVENTION
[0003] The invention described herein relates to a gene and its
encoded protein, termed 151P3D4, expressed in certain cancers, and
to diagnostic and therapeutic methods and compositions useful in
the management of cancers that express 151P3D4.
BACKGROUND OF THE INVENTION
[0004] Cancer is the second leading cause of human death next to
coronary disease. Worldwide, millions of people die from cancer
every year. In the United States alone, as reported by the American
Cancer Society, cancer causes the death of well over a half-million
people annually, with over 1.2 million new cases diagnosed per
year. While deaths from heart disease have been declining
significantly, those resulting from cancer generally are on the
rise. In the early part of the next century, cancer is predicted to
become the leading cause of death.
[0005] Worldwide, several cancers stand out as the leading killers.
In particular, carcinomas of the lung, prostate, breast, colon,
pancreas, and ovary represent the primary causes of cancer death.
These and virtually all other carcinomas share a common lethal
feature. With very few exceptions, metastatic disease from a
carcinoma is fatal. Moreover, even for those cancer patients who
initially survive their primary cancers, common experience has
shown that their lives are dramatically altered. Many cancer
patients experience strong anxieties driven by the awareness of the
potential for recurrence or treatment failure. Many cancer patients
experience physical debilitations following treatment. Furthermore,
many cancer patients experience a recurrence.
[0006] Worldwide, prostate cancer is the fourth most prevalent
cancer in men. In North America and Northern Europe, it is by far
the most common cancer in males and is the second leading cause of
cancer death in men. In the United States alone, well over 30,000
men die annually of this disease-second only to lung cancer.
Despite the magnitude of these figures, there is still no effective
treatment for metastatic prostate cancer. Surgical prostatectomy,
radiation therapy, hormone ablation therapy, surgical castration
and chemotherapy continue to be the main treatment modalities.
Unfortunately, these treatments are ineffective for many and are
often associated with undesirable consequences.
[0007] On the diagnostic front, the lack of a prostate tumor marker
that can accurately detect early-stage, localized tumors remains a
significant limitation in the diagnosis and management of this
disease. Although the serum prostate specific antigen (PSA) assay
has been a very useful tool, however its specificity and general
utility is widely regarded as lacking in several important
respects.
[0008] Progress in identifying additional specific markers for
prostate cancer has been improved by the generation of prostate
cancer xenografts that can recapitulate different stages of the
disease in mice. The LAPC (Los Angeles Prostate Cancer) xenografts
are prostate cancer xenografts that have survived passage in severe
combined immune deficient (SCID) mice and have exhibited the
capacity to mimic the transition from androgen dependence to
androgen independence (Klein et al., 1997, Nat. Med. 3:402). More
recently identified prostate cancer markers include PCTA-1 (Su et
al., 1996, Proc. Natl. Acad. Sci. USA 93: 7252), prostate-specific
membrane (PSM) antigen (Pinto et al., Clin Cancer Res Sep. 2, 1996
(9): 1445-51), STEAP (Hubert, et al., Proc Natl Acad Sci USA. Dec.
7, 1999; 96(25): 14523-8) and prostate stem cell antigen (PSCA)
(Reiter et al., 1998, Proc. Natl. Acad. Sci. USA 95: 1735).
[0009] While previously identified markers such as PSA, PSM, PCTA
and PSCA have facilitated efforts to diagnose and treat prostate
cancer, there is need for the identification of additional markers
and therapeutic targets for prostate and related cancers in order
to further improve diagnosis and therapy.
[0010] Renal cell carcinoma (RCC) accounts for approximately 3
percent of adult malignancies. Once adenomas reach a diameter of 2
to 3 cm, malignant potential exists. In the adult, the two
principal malignant renal tumors are renal cell adenocarcinoma and
transitional cell carcinoma of the renal pelvis or ureter. The
incidence of renal cell adenocarcinoma is estimated at more than
29,000 cases in the United States, and more than 11,600 patients
died of this disease in 1998. Transitional cell carcinoma is less
frequent, with an incidence of approximately 500 cases per year in
the United States.
[0011] Surgery has been the primary therapy for renal cell
adenocarcinoma for many decades. Until recently, metastatic disease
has been refractory to any systemic therapy. With recent
developments in systemic therapies, particularly immunotherapies,
metastatic renal cell carcinoma may be approached aggressively in
appropriate patients with a possibility of durable responses.
Nevertheless, there is a remaining need for effective therapies for
these patients.
[0012] Of all new cases of cancer in the United States, bladder
cancer represents approximately 5 percent in men (fifth most common
neoplasm) and 3 percent in women (eighth most common neoplasm). The
incidence is increasing slowly, concurrent with an increasing older
population. In 1998, there was an estimated 54,500 cases, including
39,500 in men and 15,000 in women. The age-adjusted incidence in
the United States is 32 per 100,000 for men and 8 per 100,000 in
women. The historic male/female ratio of 3:1 may be decreasing
related to smoking patterns in women. There were an estimated
11,000 deaths from bladder cancer in 1998 (7,800 in men and 3,900
in women). Bladder cancer incidence and mortality strongly increase
with age and will be an increasing problem as the population
becomes more elderly.
[0013] Most bladder cancers recur in the bladder. Bladder cancer is
managed with a combination of transurethral resection of the
bladder (TUR) and intravesical chemotherapy or immunotherapy. The
multifocal and recurrent nature of bladder cancer points out the
limitations of TUR. Most muscle-invasive cancers are not cured by
TUR alone. Radical cystectomy and urinary diversion is the most
effective means to eliminate the cancer but carry an undeniable
impact on urinary and sexual function. There continues to be a
significant need for treatment modalities that are beneficial for
bladder cancer patients.
[0014] An estimated 130,200 cases of colorectal cancer occurred in
2000 in the United States, including 93,800 cases of colon cancer
and 36,400 of rectal cancer. Colorectal cancers are the third most
common cancers in men and women. Incidence rates declined
significantly during 1992-1996 (-2.1% per year). Research suggests
that these declines have been due to increased screening and polyp
removal, preventing progression of polyps to invasive cancers.
There were an estimated 56,300 deaths (47,700 from colon cancer,
8,600 from rectal cancer) in 2000, accounting for about 11% of all
U.S. cancer deaths.
[0015] At present, surgery is the most common form of therapy for
colorectal cancer, and for cancers that have not spread, it is
frequently curative. Chemotherapy, or chemotherapy plus radiation,
is given before or after surgery to most patients whose cancer has
deeply perforated the bowel wall or has spread to the lymph nodes.
A permanent colostomy (creation of an abdominal opening for
elimination of body wastes) is occasionally needed for colon cancer
and is infrequently required for rectal cancer. There continues to
be a need for effective diagnostic and treatment modalities for
colorectal cancer.
[0016] There were an estimated 164,100 new cases of lung and
bronchial cancer in 2000, accounting for 14% of all U.S. cancer
diagnoses. The incidence rate of lung and bronchial cancer is
declining significantly in men, from a high of 86.5 per 100,000 in
1984 to 70.0 in 1996. In the 1990s, the rate of increase among
women began to slow. In 1996, the incidence rate in women was 42.3
per 100,000.
[0017] Lung and bronchial cancer caused an estimated 156,900 deaths
in 2000, accounting for 28% of all cancer deaths. During 1992-1996,
mortality from lung cancer declined significantly among men (-1.7%
per year) while rates for women were still significantly increasing
(0.9% per year). Since 1987, more women have died each year of lung
cancer than breast cancer, which, for over 40 years, was the major
cause of cancer death in women. Decreasing lung cancer incidence
and mortality rates most likely resulted from decreased smoking
rates over the previous 30 years; however, decreasing smoking
patterns among women lag behind those of men. Of concern, although
the declines in adult tobacco use have slowed, tobacco use in youth
is increasing again.
[0018] Treatment options for lung and bronchial cancer are
determined by the type and stage of the cancer and include surgery,
radiation therapy, and chemotherapy. For many localized cancers,
surgery is usually the treatment of choice. Because the disease has
usually spread by the time it is discovered, radiation therapy and
chemotherapy are often needed in combination with surgery.
Chemotherapy alone or combined with radiation is the treatment of
choice for small cell lung cancer; on this regimen, a large
percentage of patients experience remission, which in some cases is
long lasting. There is however, an ongoing need for effective
treatment and diagnostic approaches for lung and bronchial
cancers.
[0019] An estimated 182,800 new invasive cases of breast cancer
were expected to occur among women in the United States during
2000. Additionally, about 1,400 new cases of breast cancer were
expected to be diagnosed in men in 2000. After increasing about 4%
per year in the 1980s, breast cancer incidence rates in women have
leveled off in the 1990s to about 110.6 cases per 100,000.
[0020] In the United States alone, there were an estimated 41,200
deaths (40,800 women, 400 men) in 2000 due to breast cancer. Breast
cancer ranks second among cancer deaths in women. According to the
most recent data, mortality rates declined significantly during
1992-1996 with the largest decreases in younger women, both white
and black. These decreases were probably the result of earlier
detection and improved treatment.
[0021] Taking into account the medical circumstances and the
patient's preferences, treatment of breast cancer may involve
lumpectomy (local removal of the tumor) and removal of the lymph
nodes under the arm; mastectomy (surgical removal of the breast)
and removal of the lymph nodes under the arm; radiation therapy;
chemotherapy; or hormone therapy. Often, two or more methods are
used in combination. Numerous studies have shown that, for early
stage disease, long-term survival rates after lumpectomy plus
radiotherapy are similar to survival rates after modified radical
mastectomy. Significant advances in reconstruction techniques
provide several options for breast reconstruction after mastectomy.
Recently, such reconstruction has been done at the same time as the
mastectomy.
[0022] Local excision of ductal carcinoma in situ (DCIS) with
adequate amounts of surrounding normal breast tissue may prevent
the local recurrence of the DCIS. Radiation to the breast and/or
tamoxifen may reduce the chance of DCIS occurring in the remaining
breast tissue. This is important because DCIS, if left untreated,
may develop into invasive breast cancer. Nevertheless, there are
serious side effects or sequelae to. these treatments. There is,
therefore, a need for efficacious breast cancer treatments.
[0023] There were an estimated 23,100 new cases of ovarian cancer
in the United States in 2000. It accounts for 4% of all cancers
among women and ranks second among gynecologic cancers. During
1992-1996, ovarian cancer incidence rates were significantly
declining. Consequent to ovarian cancer, there were an estimated
14,000 deaths in 2000. Ovarian cancer causes more deaths than any
other cancer of the female reproductive system.
[0024] Surgery, radiation therapy, and chemotherapy are treatment
options for ovarian cancer. Surgery usually includes the removal of
one or both ovaries, the fallopian tubes (salpingo-oophorectomy),
and the uterus (hysterectomy). In some very early tumors, only the
involved ovary will be removed, especially in young women who wish
to have children. In advanced disease, an attempt is made to remove
all intra-abdominal disease to enhance the effect of chemotherapy.
There continues to be an important need for effective treatment
options for ovarian cancer.
[0025] There were an estimated 28,300 new cases of pancreatic
cancer in the United States in 2000. Over the past 20 years, rates
of pancreatic cancer have declined in men. Rates among women have
remained approximately constant but may be beginning to decline.
Pancreatic cancer caused an estimated 28,200 deaths in 2000 in the
United States. Over the past 20 years, there has been a slight but
significant decrease in mortality rates among men (about -0.9% per
year) while rates have increased slightly among women.
[0026] Surgery, radiation therapy, and chemotherapy are treatment
options for pancreatic cancer. These treatment options can extend
survival and/or relieve symptoms in many patients but are not
likely to produce a cure for most. There is a significant need for
additional therapeutic and diagnostic options for pancreatic
cancer.
SUMMARY OF THE INVENTION
[0027] The present invention relates to a gene, designated 151P3D4,
that has now been found to be over-expressed in the cancer(s)
listed in Table I. Northern blot expression analysis of 151P3D4
gene expression in normal tissues shows a restricted expression
pattern in adult tissues. The nucleotide (FIG. 2) and amino acid
(FIG. 2, and FIG. 3) sequences of 151P3D4 are provided. The
tissue-related profile of 151P3D4 in normal adult tissues, combined
with the over-expression observed in the tissues listed in Table I,
shows that 151P3D4 is aberrantly over-expressed in at least some
cancers, and thus serves as a useful diagnostic, prophylactic,
prognostic, and/or therapeutic target for cancers of the tissue(s)
such as those listed in Table I.
[0028] The invention provides polynucleotides corresponding or
complementary to all or part of the 151P3D4 genes, mRNAs, and/or
coding sequences, preferably in isolated form, including
polynucleotides encoding 151P3D4-related proteins and fragments of
4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,
22, 23, 24, 25, or more than 25 contiguous amino acids; at least
30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 85, 90, 95, 100 or more
than 100 contiguous amino acids of a 151P3D4-related protein, as
well as the peptides/proteins themselves; DNA, RNA, DNA/RNA
hybrids, and related molecules, polynucleotides or oligonucleotides
complementary or having at least a 90% homology to the 151P3D4
genes or mRNA sequences or parts thereof, and polynucleotides or
oligonucleotides that hybridize to the 151P3D4 genes, mRNAs, or to
151P3D4-encoding polynucleotides. Also provided are means for
isolating cDNAs and the genes encoding 151P3D4. Recombinant DNA
molecules containing 151P3D4 polynucleotides, cells transformed or
transduced with such molecules, and host-vector systems for the
expression of 151P3D4 gene products are also provided. The
invention further provides antibodies that bind to 151P3D4 proteins
and polypeptide fragments thereof, including polyclonal and
monoclonal antibodies, murine and other mammalian antibodies,
chimeric antibodies, humanized and fully human antibodies, and
antibodies labeled with a detectable marker or therapeutic agent.
In certain embodiments there is a proviso that the entire nucleic
acid sequence of FIG. 2 is not encoded and/or the entire amino acid
sequence of FIG. 2 is not prepared. In certain embodiments, the
entire nucleic acid sequence of FIG. 2 is encoded and/or the entire
amino acid sequence of FIG. 2 is prepared, either of which are in
respective human unit dose forms.
[0029] The invention further provides methods for detecting the
presence and status of 151P3D4 polynucleotides and proteins in
various biological samples, as well as methods for identifying
cells that express 151P3D4. A typical embodiment of this invention
provides methods for monitoring 151P3D4 gene products in a tissue
or hematology sample having or suspected of having some form of
growth dysregulation such as cancer.
[0030] The invention further provides various immunogenic or
therapeutic compositions and strategies for treating cancers that
express 151P3D4 such as cancers of tissues listed in Table I,
including therapies aimed at inhibiting the transcription,
translation, processing or function of 151P3D4 as well as cancer
vaccines. In one aspect, the invention provides compositions, and
methods comprising them, for treating a cancer that expresses
151P3D4 in a human subject wherein the composition comprises a
carrier suitable for human use and a human unit dose of one or more
than one agent that inhibits the production or function of 151P3D4.
Preferably, the carrier is a uniquely human carrier. In another
aspect of the invention, the agent is a moiety that is
immunoreactive with 151P3D4 protein. Non-limiting examples of such
moieties include, but are not limited to, antibodies (such as
single chain, monoclonal, polyclonal, humanized, chimeric, or human
antibodies), functional equivalents thereof (whether naturally
occurring or synthetic), and combinations thereof. The antibodies
can be conjugated to a diagnostic or therapeutic moiety. In another
aspect, the agent is a small molecule as defined herein.
[0031] In another aspect, the agent comprises one or more than one
peptide which comprises a cytotoxic T lymphocyte (CTL) epitope that
binds an HLA class I molecule in a human to elicit a CTL response
to 151P3D4 and/or one or more than one peptide which comprises a
helper T lymphocyte (HTL) epitope which binds an HLA class II
molecule in a human to elicit an HTL response. The peptides of the
invention may be on the same or on one or more separate polypeptide
molecules. In a further aspect of the invention, the agent
comprises one or more than one nucleic acid molecule that expresses
one or more than one of the CTL or HTL response stimulating
peptides as described above. In yet another aspect of the
invention, the one or more than one nucleic acid molecule may
express a moiety that is immunologically reactive with 151P3D4 as
described above. The one or more than one nucleic acid molecule may
also be, or encodes, a molecule that inhibits production of
151P3D4. Non-limiting examples of such molecules include, but are
not limited to, those complementary to a nucleotide sequence
essential for production of 151P3D4 (e.g. antisense sequences or
molecules that form a triple helix with a nucleotide double helix
essential for 151P3D4 production) or a ribozyme effective to lyse
151P3D4 mRNA.
[0032] Another embodiment of the invention is antibody epitopes
which comprise a peptide regions, or an oligonucleotide encoding
the peptide region, that has one two, three, four, or five of the
following characteristics:
[0033] i) a peptide region of at least 5 amino acids of a
particular peptide of FIG. 3, in any whole number increment up to
the full length of that protein in FIG. 3, that includes an amino
acid position having a value equal to or greater than 0.5, 0.6,
0.7, 0.8, 0.9, or having a value equal to 1.0, in the
Hydrophilicity profile of FIG. 5;
[0034] ii) a peptide region of at least 5 amino acids of a
particular peptide of FIG. 3, in any whole number increment up to
the full length of that protein in FIG. 3, that includes an amino
acid position having a value equal to or less than 0.5, 0.4, 0.3,
0.2, 0.1, or having a value equal to 0.0, in the Hydropathicity
profile of FIG. 6;
[0035] iii) a peptide region of at least 5 amino acids of a
particular peptide of FIG. 3, in any whole number increment up to
the full length of that protein in FIG. 3, that includes an amino
acid position having a value equal to or greater than 0.5, 0.6,
0.7, 0.8, 0.9, or having a value equal to 1.0, in the Percent
Accessible Residues profile of FIG. 7;
[0036] iv) a peptide region of at least 5 amino acids of a
particular peptide of FIG. 3, in any whole number increment up to
the full length of that protein in FIG. 3, that includes an amino
acid position having a value equal to or greater than 0.5, 0.6,
0.7, 0.8, 0.9, or having a value equal to 1.0, in the Average
Flexibility profile of FIG. 8; or
[0037] v) a peptide region of at least 5 amino acids of a
particular peptide of FIG. 3, in any whole number increment up to
the full length of that protein in FIG. 3, that includes an amino
acid position having a value equal to or greater than 0.5, 0.6,
0.7, 0.8, 0.9, or having a value equal to 1.0, in the Beta-turn
profile of FIG. 9.
BRIEF DESCRIPTION OF THE FIGURES
[0038] FIG. 1. The 151P3D4 SSH sequence of 417 nucleotides.
[0039] FIG. 2. The cDNA (SEQ ID. NO.:______) and amino acid
sequence (SEQ ID. NO.:______) of 151P3D4 v.1 clone 1-placenta (also
called "151P3D4 v.1" or "151P3D4 variant 1") is shown in FIG. 2A.
The start methionine is underlined. The open reading frame extends
from nucleic acid 316-1380 including the stop codon. The cDNA (SEQ
ID. NO.:______) and amino acid sequence (SEQ ID. NO.:______) of
151P3D4 variant 2 (also called "151P3D4 v.2") is shown in FIG. 2B.
The codon for the start methionine is underlined. The open reading
frame extends from nucleic acid 1-2166 including the stop codon.
The cDNA (SEQ ID. NO.:______) and amino acid sequence (SEQ ID.
NO.:______) of 151P3D4 variant 3 (also called "151P3D4 v.3") is
shown in FIG. 2C. The codon for the start methionine is underlined.
The open reading frame extends from nucleic acid 316-1380 including
the stop codon. The cDNA (SEQ ID. NO.:______) and amino acid
sequence (SEQ ID. NO.:______) of 151P3D4 variant 4 (also called
"151P3D4 v.4") is shown in FIG. 2D. The codon for the start
methionine is underlined. The open reading frame extends from
nucleic acid 316-1380 including the stop codon. The cDNA (SEQ ID.
NO.:______) and amino acid sequence (SEQ ID. NO.:______) of 151P3D4
variant 5 (also called "151P3D4 v.5") is shown in FIG. 2E. The
codon for the start methionine is underlined. The open reading
frame extends from nucleic acid 316-1380 including the stop codon.
The cDNA (SEQ ID. NO.:______) and amino acid sequence (SEQ ID.
NO.:______) of 151P3D4 variant 6 (also called "151P3D4 v.6") is
shown in FIG. 2F. The codon for the start methionine is underlined.
The open reading frame extends from nucleic acid 316-1380 including
the stop codon. The cDNA (SEQ ID. NO.:______) and amino acid
sequence (SEQ ID. NO.:______) of 151P3D4 variant 7 (also called
"151P3D4 v.7") is shown in FIG. 2G. The codon for the start
methionine is underlined. The open reading frame extends from
nucleic acid 316-1380 including the stop codon. The cDNA (SEQ ID.
NO.:______) and amino acid sequence (SEQ ID. NO.:______) of 151P3D4
variant 8 (also called "151P3D4 v.8") is shown in FIG. 2H. The
codon for the start methionine is underlined. The open reading
frame extends from nucleic acid 316-1380 including the stop codon.
The cDNA (SEQ ID. NO.:______) and amino acid sequence (SEQ ID.
NO.:______) of 151P3D4 variant 9 (also called "151P3D4 v.9") is
shown in FIG. 2I. The codon for the start methionine is underlined.
The open reading frame extends from nucleic acid 316-1380 including
the stop codon. The cDNA (SEQ ID. NO.:______) and amino acid
sequence (SEQ ID. NO.:______) of 151P3D4 variant 10 (also called
"151P3D4 v.10") is shown in FIG. 2J. The codon for the start
methionine is underlined. The open reading frame extends from
nucleic acid 316-1380 including the stop codon. The cDNA (SEQ ID.
NO.:______) and amino acid sequence (SEQ ID. NO.:______) of 151P3D4
variant 11 (also called "151P3D4 v.11") is shown in FIG. 2K. The
codon for the start methionine is underlined. The open reading
frame extends from nucleic acid 316-1380 including the stop codon.
As used herein, a reference to 151P3D4 includes all variants
thereof, including those shown in FIGS. 10 and 12.
[0040] FIG. 3. Amino acid sequence of 151P3D4 v.1 (SEQ ID.
NO.:______) is shown in FIG. 3A; it has 354 amino acids. The amino
acid sequence of 151P3D4 v.2 (SEQ ID. NO.:______) is shown in FIG.
3B; it has 721 amino acids. As used herein, a reference to 151P3D4
includes all variants thereof, including those shown in FIGS. 11
and 12.
[0041] FIG. 4. The nucleic acid sequence alignment of 151P3D4 v.1
with the mRNA for human cartilage link protein is shown in FIG. 4A.
The amino acid sequence alignments of 151P3D4 v.1 with human
cartilage link protein (4B), mouse cartilage link protein (4C),
151P3D4 v.2 (4D), hypothetical protein XP.sub.--094318 (4E), bovine
cartilage link protein (4F), and rat cartilage link protein (4G)
are shown in FIGS. 4B-4G. The amino acid sequence alignments of
151P3D4 v.2 with human cartilage link protein is shown in FIG. 4H.
The clustal alignment of 151P3D4 v.1 and 151P3D4 v.2 is shown in
FIG. 4I.
[0042] FIG. 5. Hydrophilicity amino acid profile of A) 151P3D4 v.1
and B) 151P3D4 v.2, determined by computer algorithm sequence
analysis using the method of Hopp and Woods (Hopp T. P., Woods K.
R., 1981. Proc. Natl. Acad. Sci. U.S.A. 78:3824-3828) accessed on
the Protscale website (www.expasy.ch/cgi-bin/protscale.pl) through
the ExPasy molecular biology server.
[0043] FIG. 6. Hydropathicity amino acid profile of A) 151P3D4 v.1
and B) 151P3D4 v.2, determined by computer algorithm sequence
analysis using the method of Kyte and Doolittle (Kyte J., Doolittle
R. F., 1982. J. Mol. Biol. 157:105-132) accessed on the ProtScale
website (www.expasy.ch/cgi-bin/protscale.pl) through the ExPasy
molecular biology server.
[0044] FIG. 7. Percent accessible residues amino acid profile of A)
151P3D4 v.1 and B) 151P3D4 v.2, determined by computer algorithm
sequence analysis using the method of Janin (Janin J., 1979 Nature
277:491-492) accessed on the ProtScale website
(www.expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecular
biology server.
[0045] FIG. 8. Average flexibility amino acid profile of A) 151P3D4
v.1 and B) 151P3D4 v.2, determined by computer algorithm sequence
analysis using the method of Bhaskaran and Ponnuswamy (Bhaskaran
R., and Ponnuswamy P. K., 1988. Int. J. Pept. Protein Res.
32:242-255) accessed on the ProtScale website
(www.expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecular
biology server.
[0046] FIG. 9. Beta-turn amino acid profile of A) 151P3D4 v.1 and
B) 151P3D4 v.2, determined by computer algorithm sequence analysis
using the method of Deleage and Roux (Deleage, G., Roux B. 1987
Protein Engineering 1:289-294) accessed on the ProtScale website
(www.expasy.ch/cgi-bin/prots- cale.pl) through the ExPasy molecular
biology server.
[0047] FIG. 10. Schematic display of nucleotide variants of
151P3D4. Schematic alignment of Single Nucleotide Polymorphism(SNP)
variants of 151P3D4. Variants 151P3D4 v.3 through v.11are variants
with single nucleotide differences. Though these SNP variants are
shown separately, they could also occur in any combinations and in
any one of the transcript variants that contains the base pairs.
Numbers correspond to those of 151P3D4 v.1. The black boxes show
the same sequence as 151P3D4 v.1 . SNPs are indicate the boxes.
[0048] FIG. 11. Schematic alignment of protein variants of 151P3D4.
Nucleotide variants 151P3D4 v.2 through v.9 in FIG. 10 code for the
same protein as 151P3D4 v.1. Variants 151P3D4 v.2 codes for a
protein that shares 321 aa with 151P3D4 v.1. Boxes with the same
fill pattern represent the same sequence. Numbers in "( )"
underneath the boxes correspond to 151P3D4 v.1.
[0049] FIG. 12. Schematic alignment of transcript variants of
151P3D4. Variant 151P3D4 v.2 is an alternative transcript, which
shares the last three exons with 151P3D4 v.1. The first two exons
of 151P3D4 v.1 are located in the sixth intron (between exons 6 and
7) of 151P3D4 v.2. Numbers in "( )" underneath the boxes correspond
to those of 151P3D4 v.2. Boxes with the same fill pattern represent
the same sequence.
[0050] FIG. 13. Secondary structure prediction for 151P3D4 protein
variants. The secondary structure of 151P3D4 protein variants 1 and
2 (FIGS. A and B, respectively) were predicted using the
HNN--Hierarchical Neural Network method (Guermeur, 1997,
http://pbil.ibcp.fr/cgi-bin/npsa.s-
ub.13automat.pl?page=npsa_nn.html), accessed from the ExPasy
molecular biology server (http://www.expasy.ch/tools/). This method
predicts the presence and location of alpha helices, extended
strands, and random coils from the primary protein sequence. The
percent of the protein in a given secondary structure is also
listed.
[0051] FIG. 14. Expression of 151P3D4 by RT-PCR. First strand cDNA
was prepared from vital pool 1 (liver, lung and kidney), vital pool
2 (pancreas, colon and stomach), bladder cancer pool, kidney cancer
pool, colon cancer pool, lung cancer pool, ovary cancer pool,
breast cancer pool, and cancer metastasis pool. Normalization was
performed by PCR using primers to actin and GAPDH.
Semi-quantitative PCR, using primers to 151P3D4, was performed at
26 and 30 cycles of amplification. Results show strong expression
of. 151P3D4 in ovary cancer pool. Expression of 151P3D4 was also
detected in bladder cancer pool, kidney cancer pool, colon cancer
pool, lung cancer pool, breast cancer pool, cancer metastasis pool,
vital pool 2, but not in vital pool 1.
[0052] FIG. 15. Expression of 151P3D4 in normal tissues. Two
multiple tissue northern blots (Clontech) both with 2 ug of
mRNA/lane were probed with the 151P3D4 sequence. Size standards in
kilobases (kb) are indicated on the side. Results show expression
of 151P3D4 in small intestine and placenta. Lower level expression
was also detected in heart and colon, but not in the other normal
tissues tested.
[0053] FIG. 16. Expression of 151P3D4 in bladder cancer patient
tissues. RNA was extracted from normal bladder (NB), bladder cancer
cell lines (CL: UM-UC-3, J82, SCaBER), bladder cancer patient
tumors (T) and normal adjacent tissue (NAT). Northern blots with 10
ug of total RNA were probed with the 151P3D4 SSH sequence. Size
standards in kilobases are indicated on the side. Results show
expression of 151P3D4 in patient bladder cancer tissues, and in
UM-UC-3 bladder cancer cell lines, but not in normal bladder nor in
the other bladder cancer cell lines tested.
[0054] FIG. 17. Expression of 151P3D4 in kidney cancer patient
tissues. RNA was extracted from kidney cancer cell lines (CL:
769-P, A498, SW839), normal kidney (NK), kidney cancer patient
tumors (T) and their normal adjacent tissues (NAT). Northern blots
with 10 ug of total RNA were probed with the 151P3D4 SSH sequence.
Size standards in kilobases are on the side. Results show
expression of 151P3D4 in patient kidney tumor tissues, but not in
normal kidney, nor in the cell lines tested.
[0055] FIG. 18. Expression of 151P3D4 in ovary cancer patient
tissues. RNA was extracted from ovary and cervical cancer cell
lines (CL), normal ovary (N), and ovary cancer patient tumor (T).
Northern blots with 10 ug of total RNA were probed with the 151P3D4
SSH sequence. Size standards in kilobases are on the side. Results
show strong expression of 151P3D4 in patient ovary cancer tissues,
but not in normal ovary nor in the ovary and cervical cancer cell
lines.
[0056] FIG. 19. Expression of 151P3D4 in stomach and uterus human
cancer specimens. Expression of 151P3D4 was assayed in a panel of
human stomach and uterus cancers (T) and their respective matched
normal tissues (N) on RNA dot blots. 151P3D4 expression was seen in
both stomach and uterus cancers.
[0057] FIG. 20. 151P3D4 expression in 293T cells following
transfection. 293T cells were transfected with either 151P3D4
.pcDNA3.1/mychis or pcDNA3.1/mychis vector control. Forty hours
later, cell lysates were collected. Samples were run on an SDS-PAGE
acrylamide gel, blotted and stained with anti-his antibody. The
blot was developed using the ECL chemiluminescence kit and
visualized by autoradiography. Results show expression of 151P3D4
from the 151P3D4. pcDNA3.1 /mychis mammalian expression construct
in the lysates of 151P3D4. pcDNA3.1/mychis transfected cells, but
not from the control pcDNA3.1/mychis vector.
DETAILED DESCRIPTION OF THE INVENTION
[0058] Outline of Sections
[0059] I.) Definitions
[0060] II.) 151P3D4 Polynucleotides
[0061] II.A.) Uses of 151P3D4 Polynucleotides
[0062] II.A.1.) Monitoring of Genetic Abnormalities
[0063] II.A.2.) Antisense Embodiments
[0064] II.A.3.) Primers and Primer Pairs
[0065] II.A.4.) Isolation of 151P3D4-Encoding Nucleic Acid
Molecules
[0066] II.A.5.) Recombinant Nucleic Acid Molecules and Host-Vector
Systems
[0067] III.) 151P3D4-related Proteins
[0068] III.A.) Motif-bearing Protein Embodiments
[0069] III.B.) Expression of 151P3D4-related Proteins
[0070] III.C.) Modifications of 151P3D4-related Proteins
[0071] III.D.) Uses of 151P3D4-related Proteins
[0072] IV.) 151P3D4 Antibodies
[0073] V.) 151P3D4 Cellular Immune Responses
[0074] VI.) 151P3D4 Transgenic Animals
[0075] VII.) Methods for the Detection of 151P3D4
[0076] VIII.) Methods for Monitoring the Status of 151P3D4-related
Genes and Their Products
[0077] IX.) Identification of Molecules That Interact With
151P3D4
[0078] X.) Therapeutic Methods and Compositions
[0079] X.A.) Anti-Cancer Vaccines
[0080] X.B.) 151P3D4 as a Target for Antibody-Based Therapy
[0081] X.C.) 151P3D4 as a Target for Cellular Immune Responses
[0082] X.C.1. Minigene Vaccines
[0083] X.C.2. Combinations of CTL Peptides with Helper Peptides
[0084] X.C.3. Combinations of CTL Peptides with T Cell Priming
Agents
[0085] X.C.4. Vaccine Compositions Comprising DC Pulsed with CTL
and/or HTL Peptides
[0086] X.D.) Adoptive Immunotherapy
[0087] X.E.) Administration of Vaccines for Therapeutic or
Prophylactic Purposes
[0088] XI.) Diagnostic and Prognostic Embodiments of 151P3D4.
[0089] XII.) Inhibition of 151P3D4 Protein Function
[0090] XII.A.) Inhibition of 151P3D4 With Intracellular
Antibodies
[0091] XII.B.) Inhibition of 151P3D4 with Recombinant Proteins
[0092] XII.C.) Inhibition of 151P3D4 Transcription or
Translation
[0093] XII.D.) General Considerations for Therapeutic
Strategies
[0094] XIII.) KITS
[0095] I.) Definitions:
[0096] Unless otherwise defined, all terms of art, notations and
other scientific terms or terminology used herein are intended to
have the meanings commonly understood by those of skill in the art
to which this invention pertains. In some cases, terms with
commonly understood meanings are defined herein for clarity and/or
for ready reference, and the inclusion of such definitions herein
should not necessarily be construed to represent a substantial
difference over what is generally understood in the art. Many of
the techniques and procedures described or referenced herein are
well understood and commonly employed using conventional
methodology by those skilled in the art, such as, for example, the
widely utilized molecular cloning methodologies described in
Sambrook et al., Molecular Cloning: A Laboratory Manual 2nd.
edition (1989) Cold Spring Harbor Laboratory Press, Cold Spring
Harbor, N.Y. As appropriate, procedures involving the use of
commercially available kits and reagents are generally carried out
in accordance with manufacturer defined protocols and/or parameters
unless otherwise noted.
[0097] The terms "advanced prostate cancer", "locally advanced
prostate cancer", "advanced disease" and "locally advanced disease"
mean prostate cancers that have extended through the prostate
capsule, and are meant to include stage C disease under the
American Urological Association (AUA) system, stage C1-C2 disease
under the Whitmore-Jewett systemn, and stage T3-T4 and N+ disease
under the TNM (tumor, node, metastasis) system. In general surgery
is not recommended for patients with locally advanced disease, and
these patients have substantially less favorable outcomes compared
to patients having clinically localized (organ-confined) prostate
cancer. Locally advanced disease is clinically identified by
palpable evidence of induration beyond the lateral border of the
prostate, or asymmetry or induration above the prostate base.
Locally advanced prostate cancer is presently diagnosed
pathologically following radical prostatectomy if the tumor invades
or penetrates the prostatic capsule, extends into the surgical
margin, or invades the seminal vesicles.
[0098] "Altering the native glycosylation pattern" is intended for
purposes herein to mean deleting one or more carbohydrate moieties
found in native sequence 151P3D4 (either by removing the underlying
glycosylation site or by deleting the glycosylation by chemical
and/or enzymatic means), and/or adding one or more glycosylation
sites that are not present in the native sequence 151P3D4. In
addition, the phrase includes qualitative changes in the
glycosylation of the native proteins, involving a change in the
nature and proportions of the various carbohydrate moieties
present.
[0099] The term "analog" refers to a molecule which is structurally
similar or shares similar or corresponding attributes with another
molecule (e.g. a 151P3D4-related protein). For example an analog of
a 151P3D 4 protein can be specifically bound by an antibody or T
cell that specifically binds to 151P3D4.
[0100] The term "antibody" is used in the broadest sense. Therefore
an "antibody" can be naturally occurring or man-made such as
monoclonal antibodies produced by conventional hybridoma
technology. Anti-151P3D4 antibodies comprise monoclonal and
polyclonal antibodies as well as fragments containing the
antigen-binding domain and/or one or more complementarity
determining regions of these antibodies.
[0101] An "antibody fragment" is defined as at least a portion of
the variable region of the immunoglobulin molecule that binds to
its target, i.e., the antigen-binding region. In one embodiment it
specifically covers single anti-151P3D4 antibodies and clones
thereof (including agonist, antagonist and neutralizing antibodies)
and anti-151P3D4 antibody compositions with polyepitopic
specificity.
[0102] The term "codon optimized sequences" refers to nucleotide
sequences that have been optimized for a particular host species by
replacing any codons having a usage frequency of less than about
20%. Nucleotide sequences that have been optimized for expression
in a given host species by elimination of spurious polyadenylation
sequences, elimination of exon/intron splicing signals, elimination
of transposon-like repeats and/or optimization of GC content in
addition to codon optimization are referred to herein as an
"expression enhanced sequences."
[0103] The term "cytotoxic agent" refers to a substance that
inhibits or prevents the expression activity of cells, function of
cells and/or causes destruction of cells. The term is intended to
include radioactive isotopes chemotherapeutic agents, and toxins
such as small molecule toxins or enzymatically active toxins of
bacterial, fungal, plant or animal origin, including fragments
and/or variants thereof. Examples of cytotoxic agents include, but
are not limited to maytansinoids, yttrium, bismuth, ricin, ricin
A-chain, doxorubicin, daunorubicin, taxol, ethidium bromide,
mitomycin, etoposide, tenoposide, vincristine, vinblastine,
colchicine, dihydroxy anthracin dione, actinomycin, diphtheria
toxin, Pseudomonas exotoxin (PE) A, PE40, abrin, abrin A chain,
modeccin A chain, alpha-sarcin, gelonin, mitogellin, retstrictocin,
phenomycin, enomycin, curicin, crotin, calicheamicin, sapaonaria
officinalis inhibitor, and glucocorticoid and other
chemotherapeutic agents, as well as radioisotopes such as
At.sup.211, I.sup.131, I.sup.125, Y.sup.90, Re.sup.186, Re.sup.188,
Sm.sup.153, Bi.sup.212, P.sup.32 and radioactive isotopes of Lu.
Antibodies may also be conjugated to an anti-cancer pro-drug
activating enzyme capable of converting the pro-drug to its active
form.
[0104] The term "homolog" refers to a molecule which exhibits
homology to another molecule, by for example, having sequences of
chemical residues that are the same or similar at corresponding
positions.
[0105] "Human Leukocyte Antigen" or "HLA" is a human class I or
class II Major Histocompatibility Complex (MHC) protein (see, e.g.,
Stites, et al., IMMUNOLOGY, 8.sup.TH Ed., Lange Publishing, Los
Altos, Calif. (1994).
[0106] The terms "hybridize", "hybridizing", "hybridizes" and the
like, used in the context of polynucleotides, are meant to refer to
conventional hybridization conditions, preferably such as
hybridization in 50% formamide/6.times.SSC/0.1% SDS/100 .mu.g/ml
ssDNA, in which temperatures for hybridization are above 37 degrees
C. and temperatures for washing in 0.1.times.SSC/0.1% SDS are above
55 degrees C.
[0107] The phrases "isolated" or "biologically pure" refer to
material which is substantially or essentially free from components
which normally accompany the material as it is found in its native
state. Thus, isolated peptides in accordance with the invention
preferably do not contain materials normally associated with the
peptides in their in situ environment. For example, a
polynucleotide is said to be "isolated" when it is substantially
separated from contaminant polynucleotides that correspond or are
complementary to genes other than the 151P3D4 genes or that encode
polypeptides other than 151P3D4 gene product or fragments thereof.
A skilled artisan can readily employ nucleic acid isolation
procedures to obtain an isolated 151P3D4 polynucleotide. A protein
is said to be "isolated," for example, when physical, mechanical or
chemical methods are employed to remove the 151P3D4 proteins from
cellular constituents that are normally associated with the
protein. A skilled artisan can readily employ standard purification
methods to obtain an isolated l5IP3D4 protein. Alternatively, an
isolated protein can be prepared by chemical means.
[0108] The term "mammal" refers to any organism classified as a
mammal, including mice, rats, rabbits, dogs, cats, cows, horses and
humans. In one embodiment of the invention, the mammal is a mouse.
In another embodiment of the invention, the mammal is a human.
[0109] The terms "metastatic prostate cancer" and "metastatic
disease" mean prostate cancers that have spread to regional lymph
nodes or to distant sites, and are meant to include stage D disease
under the AUA system and stage TxNxM+ under the TNM system. As is
the case with locally advanced prostate cancer, surgery is
generally not indicated for patients with metastatic disease, and
hormonal (androgen ablation) therapy is a preferred treatment
modality. Patients with metastatic prostate cancer eventually
develop an androgen-refractory state within 12 to 18 months of
treatment initiation. Approximately half of these
androgen-refractory patients die within 6 months after developing
that status. The most common site for prostate cancer metastasis is
bone. Prostate cancer bone metastases are often osteoblastic rather
than osteolytic (i.e., resulting in net bone formation). Bone
metastases are found most frequently in the spine, followed by the
femur, pelvis, rib cage, skull and humerus. Other common sites for
metastasis include lymph nodes, lung, liver and brain. Metastatic
prostate cancer is typically diagnosed by open or laparoscopic
pelvic lymphadenectomy, whole body radionuclide scans, skeletal
radiography, and/or bone lesion biopsy.
[0110] The term "monoclonal antibody" refers to an antibody
obtained from a population of substantially homogeneous antibodies,
i.e., the antibodies comprising the population are identical except
for possible naturally occurring mutations that are present in
minor amounts.
[0111] A "motif", as in biological motif of a 151P3D4-related
protein, refers to any pattern of amino acids forming part of the
primary sequence of a protein, that is associated with a particular
function (e.g. protein-protein interaction, protein-DNA
interaction, etc) or modification (e.g. that is phosphorylated,
glycosylated or amidated), or localization (e.g. secretory
sequence, nuclear localization sequence, etc.) or a sequence that
is correlated with being immunogenic, either humorally or
cellularly. A motif can be either contiguous or capable of being
aligned to certain positions that are generally correlated with a
certain function or property. In the context of HLA motifs, "motif"
refers to the pattern of residues in a peptide of defined length,
usually a peptide of from about 8 to about 13 amino acids for a
class I HLA motif and from about 6 to about 25 amino acids for a
class II HLA motif, which is recognized by a particular HLA
molecule. Peptide motifs for HLA binding are typically different
for each protein encoded by each human HLA allele and differ in the
pattern of the primary and secondary anchor residues.
[0112] A "pharmaceutical excipient" comprises a material such as an
adjuvant, a carrier, pH-adjusting and buffering agents, tonicity
adjusting agents, wetting agents, preservative, and the like.
[0113] "Pharmaceutically acceptable" refers to a non-toxic, inert,
and/or composition that is physiologically compatible with humans
or other mammals.
[0114] The term "polynucleotide" means a polymeric form of
nucleotides of at least 10 bases or base pairs in length, either
ribonucleotides or deoxynucleotides or a modified form of either
type of nucleotide, and is meant to include single and double
stranded forms of DNA and/or RNA. In the art, this term if often
used interchangeably with "oligonucleotide". A polynucleotide can
comprise a nucleotide sequence disclosed herein wherein thymidine
(T), as shown for example in FIG. 2, can also be uracil (U); this
definition pertains to the differences between the chemical
structures of DNA and RNA, in particular the observation that one
of the four major bases in RNA is uracil (U) instead of thymidine
(T).
[0115] The term "polypeptide" means a polymer of at least about 4,
5, 6, 7, or 8 amino acids. Throughout the specification, standard
three letter or single letter designations for amino acids are
used. In the art, this term is often used interchangeably with
"peptide" or "protein".
[0116] An HLA "primary anchor residue" is an amino acid at a
specific position along a peptide sequence which is understood to
provide a contact point between the immunogenic peptide and the HLA
molecule. One to three, usually two, primary anchor residues within
a peptide of defined length generally defines a "motif" for an
immunogenic peptide. These residues are understood to fit in close
contact with peptide binding groove of an HLA molecule, with their
side chains buried in specific pockets of the binding groove. In
one embodiment, for example, the primary anchor residues for an HLA
class I molecule are located at position 2 (from the amino terminal
position) and at the carboxyl terminal position of a 8, 9, 10, 11,
or 12 residue peptide epitope in accordance with the invention. In
another embodiment, for example, the primary anchor residues of a
peptide that will bind an HLA class II molecule are spaced relative
to each other, rather than to the termini of a peptide, where the
peptide is generally of at least 9 amino acids in length. The
primary anchor positions for each motif and supermotif are set
forth in Table IV. For example, analog peptides can be created by
altering the presence or absence of particular residues in the
primary and/or secondary anchor positions shown in Table IV. Such
analogs are used to modulate the binding affinity and/or population
coverage of a peptide comprising a particular HLA motif or
supermotif.
[0117] A "recombinant" DNA or RNA molecule is a DNA or RNA molecule
that has been subjected to molecular manipulation in vitro.
[0118] Non-limiting examples of small molecules include compounds
that bind or interact with 151P3D4, ligands including hormones,
neuropeptides, chemokines, odorants, phospholipids, and functional
equivalents thereof that bind and preferably inhibit 151P3D4
protein function. Such non-limiting small molecules preferably have
a molecular weight of less than about 10 kDa, more preferably below
about 9, about 8, about 7, about 6, about 5 or about 4 kDa. In
certain embodiments, small molecules physically associate with, or
bind, 151P3D4 protein; are not found in naturally occurring
metabolic pathways; and/or are more soluble in aqueous than
non-aqueous solutions
[0119] "Stringency" of hybridization reactions is readily
determinable by one of ordinary skill in the art, and generally is
an empirical calculation dependent upon probe length, washing
temperature, and salt concentration. In general, longer probes
require higher temperatures for proper annealing, while shorter
probes need lower temperatures. Hybridization generally depends on
the ability of denatured nucleic acid sequences to reanneal when
complementary strands are present in an environment below their
melting temperature. The higher the degree of desired homology
between the probe and hybridizable sequence, the higher the
relative temperature that can be used. As a result, it follows that
higher relative temperatures would tend to make the reaction
conditions more stringent, while lower temperatures less so. For
additional details and explanation of stringency of hybridization
reactions, see Ausubel et al., Current Protocols in Molecular
Biology, Wiley Interscience Publishers, (1995).
[0120] "Stringent conditions" or "high stringency conditions", as
defined herein, are identified by, but not limited to, those that:
(1) employ low ionic strength and high temperature for washing, for
example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1% sodium
dodecyl sulfate at 50.degree. C.; (2) employ during hybridization a
denaturing agent, such as formamide, for example, 50% (v/v)
formamide with 0.1% bovine serum albumin/0.1% Ficoll/0.1%
polyvinylpyrrolidone/50 mM sodium phosphate buffer at pH 6.5 with
750 mM sodium chloride, 75 mM sodium citrate at 42.degree. C.; or
(3) employ 50% formamide, 5.times.SSC (0.75 M NaCl, 0.075 M sodium
citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodium
pyrophosphate, 5.times. Denhardt's solution, sonicated salmon sperm
DNA (50 .mu.g/ml), 0.1% SDS, and 10% dextran sulfate at 42.degree.
C., with washes at 42.degree. C. in 0.2.times.SSC (sodium
chloride/sodium. citrate) and 50% fornamide at 55.degree. C.,
followed by a high-stringency wash consisting of 0.1.times.SSC
containing EDTA at 55.degree. C. "Moderately stringent conditions"
are described by, but not limited to, those in Sambrook et al.,
Molecular Cloning: A Laboratory Manual, New York: Cold Spring
Harbor Press, 1989, and include the use of washing solution and
hybridization conditions (e.g., temperature, ionic strength and %
SDS) less stringent than those described above. An example of
moderately stringent conditions is overnight incubation at
37.degree. C. in a solution comprising: 20% formamide, 5.times.SSC
(150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH
7.6), 5.times. Denhardt's solution, 10% dextran sulfate, and 20
mg/mL denatured sheared salmon sperm DNA, followed by washing the
filters in 1.times.SSC at about 37-50.degree. C. The skilled
artisan will recognize how to adjust the temperature, ionic
strength, etc. as necessary to accommodate factors such as probe
length and the like.
[0121] An HLA "supermotif" is a peptide binding specificity shared
by HLA molecules encoded by two or more HLA alleles.
[0122] As used herein "to treat" or "therapeutic" and grammatically
related terms, refer to any improvement of any consequence of
disease, such as prolonged survival, less morbidity, and/or a
lessening of side effects which are the byproducts of an
alternative therapeutic modality; full eradication of disease is
not required.
[0123] A "transgenic animal" (e.g., a mouse or rat) is an animal
having cells that contain a transgene, which transgene was
introduced into the animal or an ancestor of the animal at a
prenatal, e.g., an embryonic stage. A "transgene" is a DNA that is
integrated into the genome of a cell from which a transgenic animal
develops.
[0124] As used herein, an HLA or cellular immune response "vaccine"
is a composition that contains or encodes one or more peptides of
the invention. There are numerous embodiments of such vaccines,
such as a cocktail of one or more individual peptides; one or more
peptides of the invention comprised by a polyepitopic peptide; or
nucleic acids that encode such individual peptides or polypeptides,
e.g., a minigene that encodes a polyepitopic peptide. The "one or
more peptides" can include any whole unit integer from 1-150 or
more, e.g., at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31,
32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,
49, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115,
120, 125, 130, 135, 140, 145, or 150 or more peptides of the
invention. The peptides or polypeptides can optionally be modified,
such as by lipidation, addition of targeting or other sequences.
HLA class I peptides of the invention can be admixed with, or
linked to, HLA class II peptides, to facilitate activation of both
cytotoxic T lymphocytes and helper T lymphocytes. HLA vaccines can
also comprise peptide-pulsed antigen presenting cells, e.g.,
dendritic cells.
[0125] The term "variant" refers to a molecule that exhibits a
variation from a described type or norm, such as a protein that has
one or more different amino acid residues in the corresponding
position(s) of a specifically described protein (e.g. the 151P3D4
protein shown in FIG. 2 or FIG. 3. An analog is an example of a
variant protein. Splice isoforms and single nucleotides
polymorphisms (SNPs) are further examples of variants.
[0126] The "151P3D4-related proteins" of the invention include
those specifically identified herein, as well as allelic variants,
conservative substitution variants, analogs and homologs that can
be isolated/generated and characterized without undue
experimentation following the methods outlined herein or readily
available in the art. Fusion proteins that combine parts of
different 151P3D4 proteins or fragments thereof, as well as fusion
proteins of a 151P3D4 protein and a heterologous polypeptide are
also included. Such 151P3D4 proteins are collectively referred to
as the 151P3D4-related proteins, the proteins of the invention, or
151P3D4. The term "151P3D4-related protein" refers to a polypeptide
fragment or a 151P3D4 protein sequence of 4, 5, 6, 7, 8, 9, 10, 11,
12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more
than 25 amino acids; or, at least 30, 35, 40, 45, 50, 55, 60, 65,
70, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140,
145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 225,
250, 275, 300, 325, 350, or 354 or more amino acids.
[0127] II.) 151P3D4 Polynucleotides
[0128] One aspect of the invention provides polynucleotides
corresponding or complementary to all or part of a 151P3D4 gene,
mRNA, and/or coding sequence, preferably in isolated form,
including polynucleotides encoding a 151P3D4-related protein and
fragments thereof, DNA, RNA, DNA/RNA hybrid, and related molecules,
polynucleotides or oligonucleotides complementary to a 151P3D4 gene
or mRNA sequence or a part thereof, and polynucleotides or
oligonucleotides that hybridize to a 151P3D4 gene, mRNA, or to a
151P3D4 encoding polynucleotide (collectively, "151P3D4
polynucleotides"). In all instances when referred to in this
section, T can also be U in FIG. 2.
[0129] Embodiments of a 151P3D4 polynucleotide include: a 151P3D4
polynucleotide having the sequence shown in FIG. 2, the nucleotide
sequence of 151P3D4 as shown in FIG. 2 wherein T is U; at least 10
contiguous nucleotides of a polynucleotide having the sequence as
shown in FIG. 2; or, at least 10 contiguous nucleotides of a
polynucleotide having the sequence as shown in FIG. 2 where T is U.
For example, embodiments of 151P3D4 nucleotides comprise, without
limitation:
[0130] (I) a polynucleotide comprising, consisting essentially of,
or consisting of a sequence as shown in FIG. 2 (SEQ ID NO:______),
wherein T can also be U;
[0131] (II) a polynucleotide comprising, consisting essentially of,
or consisting of the sequence as shown in FIG. 2A (SEQ ID
NO:______), from nucleotide residue number 316 through nucleotide
residue number 1380, including the stop codon, wherein T can also
be U;
[0132] (III) a polynucleotide comprising, consisting essentially
of, or consisting of the sequence as shown in FIG. 2B (SEQ ID
NO:______), from nucleotide residue number 1 through nucleotide
residue number 2166, including the stop codon, wherein T can also
be U;
[0133] (IV) a polynucleotide comprising, consisting essentially of,
or consisting of the sequences as shown in FIGS. 2C-2K (SEQ ID
NOs:______), from nucleotide residue number 316 through nucleotide
residue number 1380, including the a stop codon, wherein T can also
be U;
[0134] (V) a polynucleotide that encodes a 151P3D4-related protein
that is at least 90% homologous to an entire amino acid sequence
shown in FIGS. 2A-K (SEQ ID NO:______);
[0135] (VI) a polynucleotide that encodes a 151P3D4-related protein
that is at least 90% identical to an entire amino acid sequence
shown in FIGS. 2A-K (SEQ ID NO:______);
[0136] (VII) a polynucleotide that encodes at least one peptide set
forth in Tables V-XVIII and XXII-LI;
[0137] (VIII) a polynucleotide that encodes a peptide region of at
least 5 amino acids of a peptide of FIG. 3A in any whole number
increment up to 354 that includes an amino acid position having a
value greater than 0.5 in the Hydrophilicity profile of FIG. 5A; or
of FIG. 3B in any whole number increment up to 721 that includes an
amino acid position having a value greater than 0.5 in the
Hydrophilicity profile of FIG. 5B;
[0138] (XIX) a polynucleotide that encodes a peptide region of at
least 5 amino acids of a peptide of FIG. 3A in any whole number
increment up to 354 that includes an amino acid position having a
value less than 0.5 in the Hydropathicity profile of FIG. 6A; or of
FIG. 3B in any whole number increment up to 721 that includes an
amino acid position having a value less than 0.5 in the
Hydropathicity profile of FIG. 6B;
[0139] (X) a polynucleotide that encodes a peptide region of at
least 5 amino acids of a peptide of FIG. 3A in any whole number
increment up to 354 that includes an amino acid position having a
value greater than 0.5 in the Percent Accessible Residues profile
of FIG. 7A; or of FIG. 3B in any whole number increment up to 721
that includes an amino acid position having a value greater than
0.5 in the Percent Accessible Residues profile of FIG. 7B;
[0140] (XII) a polynucleotide that encodes a peptide region of at
least 5 amino acids of a peptide of FIG. 3A in any whole number
increment up to 354 that includes an amino acid position having a
value greater than 0.5 in the Average Flexibility profile of FIG.
8A; or of FIG. 3B in any whole number increment up to 721 that
includes an amino acid position having a value greater than 0.5 in
the Average Flexibility profile of FIG. 8B;
[0141] (XIII) a polynucleotide that encodes a peptide region of at
least 5 amino acids of a peptide of FIG. 3A in any whole number
increment up to 354 that includes an amino acid position having a
value greater than 0.5 in the Beta-turn profile of FIG. 9A; or of
FIG. 3B in any whole number increment up to 721 that includes an
amino acid position having a value greater than 0.5 in the
Beta-turn profile of FIG. 9B;
[0142] (XIV) a polynucleotide that is fully complementary to a
polynucleotide of any one of (I)-(XIII).
[0143] (XV) a peptide that is encoded by any of (I)-(XIV); and
[0144] (XVI) a polynucleotide of any of (I)-(XIV) or peptide of
(XV) together with a pharmaceutical excipient and/or in a human
unit dose form.
[0145] As used herein, a range is understood to specifically
disclose all whole unit positions thereof.
[0146] Typical embodiments of the invention disclosed herein
include 151P3D4 polynucleotides that encode specific portions of
151P3D4 mRNA sequences (and those which are complementary to such
sequences) such as those that encode the proteins and/or fragments
thereof, for example:
[0147] (a) 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,
19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75,
80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145,
150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 225, 250,
275, 300, 325, 350, or 354 or more contiguous amino acids of
151P3D4.
[0148] (b) 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,
19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75,
80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145,
150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 225, 250,
275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575,
600, 625, 650, 675, 700, or 721 or more contiguous amino acids of
151P3D4 variant 2.
[0149] For example, representative embodiments of the invention
disclosed herein include: polynucleotides and their encoded
peptides themselves encoding about amino acid 1 to about amino acid
10 of the 151P3D4 protein shown in FIG. 2 or FIG. 3,
polynucleotides encoding about amino acid 10 to about amino acid 20
of the 151P3D4 protein shown in FIG. 2 or FIG. 3, polynucleotides
encoding about amino acid 20 to about amino acid 30 of the 151P3D4
protein shown in FIG. 2 or FIG. 3, polynucleotides encoding about
amino acid 30 to about amino acid 40 of the 151P3D4 protein shown
in FIG. 2 or FIG. 3, polynucleotides encoding about amino acid 40
to about amino acid 50 of the 151P3D4 protein shown in FIG. 2 or
FIG. 3, polynucleotides encoding about amino acid 50 to about amino
acid 60 of the 151P3D4 protein shown in FIG. 2 or FIG. 3,
polynucleotides encoding about amino acid 60 to about amino acid 70
of the 151P3D4 protein shown in FIG. 2 or FIG. 3, polynucleotides
encoding about amino acid 70 to about amino acid 80 of the 151P3D4
protein shown in FIG. 2 or FIG. 3, polynucleotides encoding about
amino acid 80 to about amino acid 90 of the 151P3D4 protein shown
in FIG. 2 or FIG. 3, polynucleotides encoding about amino acid 90
to about amino acid 100 of the 151P3D4 protein shown in FIG. 2 or
FIG. 3, in increments of about 10 amino acids, ending at the
carboxyl terminal amino acid set forth in FIG. 2 or FIG. 3.
Accordingly polynucleotides encoding portions of the amino acid
sequence (of about 10 amino acids), of amino acids 100 through the
carboxyl terminal amino acid of the 151P3D4 protein are embodiments
of the invention. Wherein it is understood that each particular
amino acid position discloses that position plus or minus five
amino acid residues.
[0150] Polynucleotides encoding relatively long portions of a
151P3D4 protein are also within the scope of the invention. For
example, polynucleotides encoding from about amino acid 1 (or 20 or
30 or 40 etc.) to about amino acid 20, (or 30, or 40 or 50 etc.) of
the 151P3D4 protein "or variant" shown in FIG. 2 or FIG. 3 can be
generated by a variety of techniques well known in the art. These
polynucleotide fragments can include any portion of the 151P3D4
sequence as shown in FIG. 2.
[0151] One embodiment of the invention comprises an HLA peptide,
that occurs at least twice in Tables V-XVIII and XXII to LI
collectively, or an oligonucleotide that encodes the HLA peptide.
Another embodiment of the invention comprises an HLA peptide that
occurs at least once in Tables V-XVIII and at least once in tables
XXII to LI, or an oligonucleotide that encodes the HLA peptide. In
another embodiment of the invention, typical polynucleotide
fragments can encode one or more of the 151P3D4 protein or variant
N-glycosylation sites, cAMP and cGMP-dependent protein kinase
phosphorylation sites, casein kinase II phosphorylation sites or
N-myristoylation site and amidation sites.
[0152] II.A.) Uses of 151P3D4 Polynucleotides
[0153] II.A.1.) Monitoring of Genetic Abnormalities
[0154] The polynucleotides of the preceding paragraphs have a
number of different specific uses. The human 151P3D4 gene maps to
the chromosomal location set forth in the Example entitled
"Chromosomal Mapping of 151P3D4." For example, because the 151P3D4
gene maps to this chromosome, polynucleotides that encode different
regions of the 151P3D4 proteins are used to characterize
cytogenetic abnormalities of this chromosomal locale, such as
abnormalities that are identified as being associated with various
cancers. In certain genes, a variety of chromosomal abnormalities
including rearrangements have been identified as frequent
cytogenetic abnormalities in a number of different cancers (see
e.g. Krajinovic et al., Mutat. Res. 382(34): 81-83 (1998);
Johansson et al., Blood 86(10): 3905-3914 (1995) and Finger et al.,
P.N.A.S. 85(23): 9158-9162 (1988)). Thus, polynucleotides encoding
specific regions of the 151P3D4 proteins provide new tools that can
be used to delineate; with greater precision than previously
possible, cytogenetic abnormalities in the chromosomal region that
encodes 151P3D4 that may contribute to the malignant phenotype. In
this context, these polynucleotides satisfy a need in the art for
expanding the sensitivity of chromosomal screening in order to
identify more subtle and less common chromosomal abnormalities (see
e.g. Evans et al, Am. J. Obstet. Gynecol 171(4): 1055-1057
(1994)).
[0155] Furthermore, as 151P3D4 was shown to be highly expressed in
bladder and other cancers, 151P3D4 polynucleotides are used in
methods assessing the status of 151P3D4 gene products in normal
versus cancerous tissues. Typically, polynucleotides that encode
specific regions of the 151P3D4 proteins are used to assess the
presence of perturbations (such as deletions, insertions, point
mutations, or alterations resulting in a loss of an antigen etc.)
in specific regions of the 151P3D4 gene, such as regions containing
one or more motifs. Exemplary assays include both RT-PCR assays as
well as single-strand conformation polymorphism (SSCP) analysis
(see, e.g., Marrogi et al., J. Cutan. Pathol. 26(8): 369-378
(1999), both of which utilize polynucleotides encoding specific
regions of a protein to examine these regions within the
protein.
[0156] II.A.2.) Antisense Embodiments
[0157] Other specifically contemplated nucleic acid related
embodiments of the invention disclosed herein are genomic DNA,
cDNAs, rybozymes, and antisense molecules, as well as nucleic acid
molecules based on an alternative backbone, or including
alternative bases, whether derived from natural sources or
synthesized, and include molecules capable of inhibiting the RNA or
protein expression of 151P3D4. For example, antisense molecules can
be RNAs or other molecules, including peptide nucleic acids (PNAs)
or non-nucleic acid molecules such as phosphorothioate derivatives,
that specifically bind DNA or RNA in a base pair-dependent manner.
A skilled artisan can readily obtain these classes of nucleic acid
molecules using the 151P3D4 polynucleotides and polynucleotide
sequences disclosed herein.
[0158] Antisense technology entails the administration of exogenous
oligonucleotides that bind to a target polynucleotide located
within the cells. The term "antisense" refers to the fact that such
oligonucleotides are complementary to their intracellular targets,
e.g., 151P3D4. See for example, Jack Cohen, Oligodeoxynucleotides,
Antisense Inhibitors of Gene Expression, CRC Press, 1989; and
Synthesis 1:1-5 (1988). The 151P3D4 antisense oligonucleotides of
the present invention include derivatives such as
S-oligonucleotides (phosphorothioate derivatives or S-oligos, see,
Jack Cohen, supra), which exhibit enhanced cancer cell growth
inhibitory action. S-oligos (nucleoside phosphorothioates) are
isoelectronic analogs of an oligonucleotide (O-oligo) in which a
nonbridging oxygen atom of the phosphate group is replaced by a
sulfur atom. The S-oligos of the present invention can be prepared
by treatment of the corresponding O-oligos with
3H-1,2-benzodithiol-3-one-1,1-dioxide, which is a sulfur transfer
reagent. See, e.g., Iyer, R. P. et al., J. Org. Chem. 55:4693-4698
(1990); and Iyer, R. P. et al., J. Am. Chem. Soc. 112:1253-1254
(1990). Additional 151P3D4 antisense oligonucleotides of the
present invention include morpholino antisense oligonucleotides
known in the art (see, e.g., Partridge et al., 1996, Antisense
& Nucleic Acid Drug Development 6: 169-175).
[0159] The 151P3D4 antisense oligonucleotides of the present
invention typically can be RNA or DNA that is complementary to and
stably hybridizes with the first 100 5' codons or last 100 3'
codons of a 151P3D4 genomic sequence or the corresponding mRNA.
Absolute complementarity is not required, although high degrees of
complementarity are preferred. Use of an oligonucleotide
complementary to this region allows for the selective hybridization
to 151P3D4 mRNA and not to mRNA specifying other regulatory
subunits of protein kinase. In one embodiment, 151P3D4 antisense
oligonucleotides of the present invention are 15 to 30-mer
fragments of the antisense DNA molecule that have a sequence that
hybridizes to 151P3D4 mRNA. Optionally, 151P3D4 antisense
oligonucleotide is a 30-mer oligonucleotide that is complementary
to a region in the first 10 5' codons or last 10 3' codons of
151P3D4. Alternatively, the antisense molecules are modified to
employ ribozymes in the inhibition of 151P3D4 expression, see,
e.g., L. A. Couture & D. T. Stinchcomb; Trends Genet 12:
510-515 (1996).
[0160] II.A.3.) Primers and Primer Pairs
[0161] Further specific embodiments of this nucleotides of the
invention include primers and primer pairs, which allow the
specific amplification of polynucleotides of the invention or of
any specific parts thereof, and probes that selectively or
specifically hybridize to nucleic acid molecules of the invention
or to any part thereof. Probes can be labeled with a detectable
marker, such as, for example, a radioisotope, fluorescent compound,
bioluminescent compound, a chemiluminescent compound, metal
chelator or enzyme. Such probes and primers are used to detect the
presence of a 151P3D4 polynucleotide in a sample and as a means for
detecting a cell expressing a 151P3D4 protein.
[0162] Examples of such probes include polypeptides comprising all
or part of the human 151P3D4 cDNA sequence shown in FIG. 2.
Examples of primer pairs capable of specifically amplifping 151P3D4
mRNAs are also described in the Examples. As will be understood by
the skilled artisan, a great many different primers and probes can
be prepared based on the sequences provided herein and used
effectively to amplify and/or detect a 151P3D4 mRNA.
[0163] The 151P3D4 polynucleotides of the invention are useful for
a variety of purposes, including but not limited to their use as
probes and primers for the amplification and/or detection of the
151P3D4 gene(s), mRNA(s), or fragments thereof; as reagents for the
diagnosis and/or prognosis of prostate cancer and other cancers; as
coding sequences capable of directing the expression of 151P3D4
polypeptides; as tools for modulating or inhibiting the expression
of the 151P3D4 gene(s) and/or translation of the 151P3D4
transcript(s); and as therapeutic agents.
[0164] The present invention includes the use of any probe as
described herein to identify and isolate a 151P3D4 or 151P3D4
related nucleic acid sequence from a naturally occurring source,
such as humans or other mammals, as well as the isolated nucleic
acid sequence per se, which would comprise all or most of the
sequences found in the probe used.
[0165] II.A.4.) Isolation of 151P3D4-Encoding Nucleic Acid
Molecules
[0166] The 151P3D4 cDNA sequences described herein enable the
isolation of other polynucleotides encoding 151P3D4 gene
product(s), as well as the isolation of polynucleotides encoding
151P3D4 gene product homologs alternatively spliced isoforms,
allelic variants, and mutant forms of a 151P3D4 gene product as
well as polynucleotides that encode analogs of 151P3D4-related
proteins. Various molecular cloning methods that can be employed to
isolate full length cDNAs encoding a 151P3D4 gene are well known
(see, for example, Sambrook, J. et al., Molecular Cloning: A
Laboratory Manual, 2d edition, Cold Spring Harbor Press, New York,
1989; Current Protocols in Molecular Biology. Ausubel et al, Eds.,
Wiley and Sons, 1995). For example, lambda phage cloning
methodologies can be conveniently employed, using commercially
available cloning systems (e.g., Lambda ZAP Express, Stratagene).
Phage clones containing 151P3D4 gene cDNAs can be identified by
probing with a labeled 151P3D4 cDNA or a fragment thereof For
example, in one embodiment, a 151P3D4 cDNA (e.g., FIG. 2) or a
portion thereof can be synthesized and used as a probe to retrieve
overlapping and full-length cDNAs corresponding to a 151P3D4 gene.
A 151P3D4 gene itself can be isolated by screening genomic DNA
libraries, bacterial artificial chromosome libraries (BACs), yeast
artificial chromosome libraries (YACs), and the like, with 151P3D4
DNA probes or primers.
[0167] II.A.5.) Recombinant Nucleic Acid Molecules and Host-Vector
Systems
[0168] The invention also provides recombinant DNA or RNA molecules
containing a 151P3D4 polynucleotide, a fragment, analog or
homologue thereof, including but not limited to phages, plasmids,
phagemids, cosmids, YACs, BACs, as well as various viral and
non-viral vectors well known in the art, and cells transformed or
transfected with such recombinant DNA or RNA molecules. Methods for
generating such molecules are well known (see, for example,
Sambrook et al., 1989, supra).
[0169] The invention further provides a host-vector system
comprising a recombinant DNA molecule containing a 151P3D4
polynucleotide, fragment, analog or homologue thereof within a
suitable prokaryotic or eukaryotic host cell. Examples of suitable
eukaryotic host cells include a yeast cell, a plant cell, or an
animal cell, such as a mammalian cell or an insect cell (e.g., a
baculovirus-infectible cell such as an Sf9 or HighFive cell).
Examples of suitable mammalian cells include various prostate
cancer cell lines such as DU145 and TsuPr1, other transfectable or
transducible prostate cancer cell lines, primary cells (PrEC), as
well as a number of mammalian cells routinely used for the
expression of recombinant proteins (e.g., COS, CHO, 293, 293T
cells). More particularly, a polynucleotide comprising the coding
sequence of 151P3D4 or a fragment, analog or homolog thereof can be
used to generate 151P3D4 proteins or fragments thereof using any
number of host-vector systems routinely used and widely known in
the art.
[0170] A wide range of host-vector systems suitable for the
expression of 151P3D4 proteins or fragments thereof are available,
see for example, Sambrook et al., 1989, supra; Current Protocols in
Molecular Biology, 1995, supra). Preferred vectors for mammalian
expression include but are not limited to pcDNA 3.1 myc-His-tag
(Invitrogen) and the retroviral vector pSRA.alpha.tkneo (Muller et
al., 1991, MCB 11:1785). Using these expression vectors, 151P3D4
can be expressed in several prostate cancer and non-prostate cell
lines, including for example 293, 293T, rat-1, NIH 3T3 and TsuPr1.
The host-vector systems of the invention are useful for the
production of a 151P3D4 protein or fragment thereof. Such
host-vector systems can be employed to study the functional
properties of 151P3D4 and 151P3D4 mutations or analogs.
[0171] Recombinant human 151P3D4 protein or an analog or homolog or
fragment thereof can be produced by mammalian cells transfected
with a construct encoding a 151P3D4-related nucleotide. For
example, 293T cells can be transfected with an expression plasmid
encoding 151P3D4 or fragment, analog or homolog thereof, a
151P3D4-related protein is expressed in the 293T cells, and the
recombinant 151P3D4 protein is isolated using standard purification
methods (e.g., affinity purification using anti-151P3D4
antibodies). In another embodiment, a 151P3D4 coding sequence is
subcloned into the retroviral vector pSR.alpha.MSVtkneo and used to
infect various mammalian cell lines, such as NIH 3T3, TsuPr1, 293
and rat-1 in order to establish 151P3D4 expressing cell lines.
Various other expression systems well known in the art can also be
employed. Expression constructs encoding a leader peptide joined in
frame to a 151P3D4 coding sequence can be used for the generation
of a secreted form of recombinant 151P3D4 protein.
[0172] As discussed herein, redundancy in the genetic code permits
variation in 151P3D4 gene sequences. In particular, it is known in
the art that specific host species often have specific codon
preferences, and thus one can adapt the disclosed sequence as
preferred for a desired host. For example, preferred analog codon
sequences typically have rare codons (i.e., codons having a usage
frequency of less than about 20% in known sequences of the desired
host) replaced with higher frequency codons. Codon preferences for
a specific species are calculated, for example, by utilizing codon
usage tables available on the INTERNET such as at URL
www.dna.affrc.go.jp/.about.nakamura/codon.html.
[0173] Additional sequence modifications are known to enhance
protein expression in a cellular host. These include elimination of
sequences encoding spurious polyadenylation signals, exon/intron
splice site signals, transposon-like repeats, and/or other such
well-characterized sequences that are deleterious to gene
expression. The GC content of the sequence is adjusted to levels
average for a given cellular host, as calculated by reference to
known genes expressed in the host cell. Where possible, the
sequence is modified to avoid predicted hairpin secondary mRNA
structures. Other useful modifications include the addition of a
translational initiation consensus sequence at the start of the
open reading frame, as described in Kozak, Mol. Cell Bio.,
9:5073-5080 (1989). Skilled artisans understand that the general
rule that eukaryotic ribosomes initiate translation exclusively at
the 5' proximal AUG codon is abrogated only under rare conditions
(see, e.g., Kozak PNAS 92(7): 2662-2666, (1995) and Kozak NAR
15(20): 8125-8148 (1987)).
[0174] III.) 151P3D4Related Proteins
[0175] Another aspect of the present invention provides
151P3D4-related proteins. Specific embodiments of 151P3D4 proteins
comprise a polypeptide having all or part of the amino acid
sequence of human 151P3D4 as shown in FIG. 2 or FIG. 3.
Alternatively, embodiments of 151P3D4 proteins comprise variant,
homolog or analog polypeptides that have alterations in the amino
acid sequence of 151P3D4 shown in FIG. 2 or FIG. 3.
[0176] In general, naturally occurring allelic variants of human
151P3D4 share a high degree of structural identity and homology
(e.g., 90% or more homology). Typically, allelic variants of a
151P3D4 protein contain conservative amino acid substitutions
within the 151P3D4 sequences described herein or contain a
substitution of an amino acid from a corresponding position in a
homologue of 151P3D4. One class of 151P3D4 allelic variants are
proteins that share a high degree of homology with at least a small
region of a particular 151P3D4 amino acid sequence, but further
contain a radical departure from the sequence, such as a
non-conservative substitution, truncation, insertion or frame
shift. In comparisons of protein sequences, the terms, similarity,
identity, and homology each have a distinct meaning as appreciated
in the field of genetics. Moreover, orthology and paralogy can be
important concepts describing the relationship of members of a
given protein family in one organism to the members of the same
family in other organisms.
[0177] Amino acid abbreviations are provided in Table II.
Conservative amino acid substitutions can frequently be made in a
protein without altering either the conformation or the function of
the protein. Proteins of the invention can comprise 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15 conservative substitutions. Such
changes include substituting any of isoleucine (I), valine (V), and
leucine (L) for any other of these hydrophobic amino acids;
aspartic acid (D) for glutamic acid (E) and vice versa; glutamine
(Q) for asparagine (N) and vice versa; and serine (S) for threonine
(T) and vice versa. Other substitutions can also be considered
conservative, depending on the environment of the particular amino
acid and its role in the three-dimensional structure of the
protein. For example, glycine (G) and alanine (A) can frequently be
interchangeable, as can alanine (A) and valine (V). Methionine (M),
which is relatively hydrophobic, can frequently be interchanged
with leucine and isoleucine, and sometimes with valine. Lysine (K)
and arginine (R) are frequently interchangeable in locations in
which the significant feature of the amino acid residue is its
charge and the differing pK's of these two amino acid residues are
not significant. Still other changes can be considered
"conservative" in particular environments (see, e.g. Table III
herein; pages 13-15 "Biochemistry" 2.sup.nd ED. Lubert Stryer ed
(Stanford University); Henikoff et al., PNAS 1992 Vol 89
10915-10919; Lei et al., J Biol Chem May 19, 1995;
270(20):11882-6).
[0178] Embodiments of the invention disclosed herein include a wide
variety of art-accepted variants or analogs of 151P3D4 proteins
such as polypeptides having amino acid insertions, deletions and
substitutions. 151P3D4 variants can be made using methods known in
the art such as site-directed mutagenesis, alanine scanning, and
PCR mutagenesis. Site-directed mutagenesis (Carter et al., Nucl.
Acids Res., 13:4331 (1986); Zoller et al., Nucl. Acids Res.,
10:6487 (1987)), cassette mutagenesis (Wells et al., Gene, 34:315
(1985)), restriction selection mutagenesis (Wells et al., Philos.
Trans. R. Soc. London SerA, 317:415 (1986)) or other known
techniques can be performed on the cloned DNA to produce the
151P3D4 variant DNA.
[0179] Scanning amino acid analysis can also be employed to
identify one or more amino acids along a contiguous sequence that
is involved in a specific biological activity such as a
protein-protein interaction. Among the preferred scanning amino
acids are relatively small, neutral amino acids. Such amino acids
include alanine, glycine, serine, and cysteine. Alanine is
typically a preferred scanning amino acid among this group because
it eliminates the side-chain beyond the beta-carbon and is less
likely to alter the main-chain conformation of the variant. Alanine
is also typically preferred because it is the most common amino
acid. Further, it is frequently found in both buried and exposed
positions (Creighton, The Proteins, (W. H. Freeman & Co.,
N.Y.); Chothia, J. Mol. Biol., 150:1 (1976)). If alanine
substitution does not yield adequate amounts of variant, an
isosteric amino acid can be used.
[0180] As defined herein, 151P3D4 variants, analogs or homologs,
have the distinguishing attribute of having at least one epitope
that is "cross reactive" with a 151P3D4 protein having an amino
acid sequence of FIG. 3. As used in this sentence, "cross reactive"
means that an antibody or T cell that specifically binds to a
151P3D4 variant also specifically binds to a 151P3D4 protein having
an amino acid sequence set forth in FIG. 3. A polypeptide ceases to
be a variant of a protein shown in FIG. 3, when it no longer
contains any epitope capable of being recognized by an antibody or
T cell that specifically binds to the starting 151P3D4 protein.
Those skilled in the art understand that antibodies that recognize
proteins bind to epitopes of varying size, and a grouping of the
order of about four or five amino acids, contiguous or not, is
regarded as a typical number of amino acids in a minimal epitope.
See, e.g., Nair et al., J. Immunol 2000 165(12): 6949-6955; Hebbes
et al., Mol Immunol (1989) 26(9):865-73; Schwartz et al., J Immunol
(1985) 135(4):259
[0181] Other classes of 151P3D4-related protein variants share 70%,
75%, 80%, 85% or 90% or more similarity with an amino acid sequence
of FIG. 3, or a fragment thereof. Another specific class of 151P3D4
protein variants or analogs comprise one or more of the 151P3D4
biological motifs described herein or presently known in the art.
Thus, encompassed by the present invention are analogs of 151P3D4
fragments (nucleic or amino acid) that have altered functional
(e.g. immunogenic) properties relative to the starting fragment. It
is to be appreciated that motifs now or which become part of the
art are to be applied to the nucleic or amino acid sequences of
FIG. 2 or FIG. 3.
[0182] As discussed herein, embodiments of the claimed invention
include polypeptides containing less than the full amino acid
sequence of a 151P3D4 protein shown in FIG. 2 or FIG. 3. For
example, representative embodiments of the invention comprise
peptides/proteins having any 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
15 or more contiguous amino acids of a 151P3D4 protein shown in
FIG. 2 or FIG. 3.
[0183] Moreover, representative embodiments of the invention
disclosed herein include polypeptides consisting of about amino
acid 1 to abqut amino acid 10 of a 151P3D4 protein shown in FIG. 2
or FIG. 3, polypeptides consisting of about amino acid 10 to about
amino acid 20 of a 151P3D4 protein shown in FIG. 2 or FIG. 3,
polypeptides consisting of about amino acid 20 to about amino acid
30 of a 151P3D4 protein shown in FIG. 2 or FIG. 3, polypeptides
consisting of about amino acid 30 to about amino acid 40 of a
151P3D4 protein shown in FIG. 2 or FIG. 3, polypeptides consisting
of about amino acid 40 to about amino acid 50 of a 151P3D4 protein
shown in FIG. 2 or FIG. 3, polypeptides consisting of about amino
acid 50 to about amino acid 60 of a 151P3D4 protein shown in FIG. 2
or FIG. 3, polypeptides consisting of about amino acid 60 to about
amino acid 70 of a 151P3D4 protein shown in FIG. 2 or FIG. 3,
polypeptides consisting of about amino acid 70 to about amino acid
80 of a 151P3D4 protein shown in FIG. 2 or FIG. 3, polypeptides
consisting of about amino acid 80 to about amino acid 90 of a
151P3D4 protein shown in FIG. 2 or FIG. 3, polypeptides consisting
of about amino acid 90 to about amino acid 100 of a 151P3D4 protein
shown in FIG. 2 or FIG. 3, etc. throughout the entirety of a
151P3D4 amino acid sequence. Moreover, polypeptides consisting of
about amino acid 1 (or 20 or 30 or 40 etc.) to about amino acid 20,
(or 130, or 140 or 150 etc.) of a 151P3D4 protein shown in FIG. 2
or FIG. 3 are embodiments the invention. It is to be appreciated
that the starting and stopping positions in this paragraph refer to
the specified position as well as that position plus or minus 5
residues.
[0184] 151P3D4-related proteins are generated using standard
peptide synthesis technology or using chemical cleavage methods
well known in the art. Alternatively, recombinant methods can be
used to generate nucleic acid molecules that encode a
151P3D4-related protein. In one embodiment, nucleic acid molecules
provide a means to generate defined fragments of a 151P3D4 protein
(or variants, homologs or analogs thereof).
[0185] III.A.) Motif-Bearing Protein Embodiments
[0186] Additional illustrative embodiments of the invention
disclosed herein include 151P3D4 polypeptides comprising the amino
acid residues of one or more of the biological motifs contained
within a 151P3D4 polypeptide sequence set forth in FIG. 2 or FIG.
3. Various motifs are known in the art, and a protein can be
evaluated for the presence of such motifs by a number of publicly
available Internet sites (see, e.g., URL addresses:
pfam.wustl.edu/; http://searchlauncher.bcm.tmc.edu/seq-search/-
struc-predict.html; psort.ims.u-tokyo.ac.jp/; www.cbs.dtu.dk/;
www.ebi.ac.uk/interpro/scan.html;
www.expasy.ch/tools/scnpsit1.html; Epimatrix.TM. and Epimer.TM.,
Brown University, www.brown.edu/Research/TB-
-HIV_Lab/epimatrix/epimatrix.html; and BIMAS,
bimas.dcrt.nih.gov/.).
[0187] Motif bearing subsequences of all 151P3D4 variant proteins
are set forth and identified in Tables V-XVIII and XXII-LII.
[0188] Table XIX sets forth several frequently occurring motifs
based on pfam searches (see URL address pfam.wustl.edu/). The
columns of Table XIX list (1) motif name abbreviation, (2) percent
identity found amongst the different member of the motif family,
(3) motif name or description and (4) most common function;
location information is included if the motif is relevant for
location.
[0189] Polypeptides comprising one or more of the 151P3D4 motifs
discussed above are useful in elucidating the specific
characteristics of a malignant phenotype in view of the observation
that the 151P3D4 motifs discussed above are associated with growth
dysregulation and because 151P3D4 is overexpressed in certain
cancers (See, e.g., Table I). Casein kinase II, cAMP and
camp-dependent protein kinase, and Protein Kinase C, for example,
are enzymes known to be associated with the development of the
malignant phenotype (see e.g. Chen et al., Lab Invest., 78(2):
165-174 (1998); Gaiddon et al., Endocrinology 136(10): 4331-4338
(1995); Hall et al., Nucleic Acids Research 24(6): 1119-1126
(1996); Peterziel et al. Oncogene 18(46): 6322-6329 (1999) and
O'Brian, Oncol. Rep. 5(2): 305-309 (1998)). Moreover, both
glycosylation and myristoylation are protein modifications also
associated with cancer and cancer progression (see e.g. Dennis et
al., Biochem. Biophys. Acta 1473(1):21-34 (1999); Raju et al., Exp.
Cell Res. 235(1): 145-154 (1997)). Amidation is another protein
modification also associated with cancer and cancer progression
(see e.g. Treston et al., J. Natl. Cancer Inst. Monogr. (13):
169-175 (1992)).
[0190] In another embodiment, proteins of the invention comprise
one or more of the immunoreactive epitopes identified in accordance
with art-accepted methods, such as the peptides set forth in Tables
V-XVIII and XXII-LI. CTL epitopes can be determined using specific
algorithms to identify peptides within a 151P3D4 protein that are
capable of optimally binding to specified HLA alleles (e.g., Table
IV; Epimatrix.TM. and Epimer.TM., Brown University, URL
www.brown.edu/Research/TB-HIV_Lab/epima- trix/epimatrix.html; and
BIMAS, URL bimas.dcrt.nih.gov/.) Moreover, processes for
identifying peptides that have sufficient binding affinity for HLA
molecules and which are correlated with being immunogenic epitopes,
are well known in the art, and are carried out without undue
experimentation. In addition, processes for identifying peptides
that are immunogenic epitopes, are well known in the art, and are
carried out without undue experimentation either in vitro or in
vivo.
[0191] Also known in the art are principles for creating analogs of
such epitopes in order to modulate immunogenicity. For example, one
begins with an epitope that bears a CTL or HTL motif (see, e.g.,
the HLA Class I and HLA Class II motifs/supermotifs of Table IV).
The epitope is analoged by substituting out an amino acid at one of
the specified positions, and replacing it with another amino acid
specified for that position. For example, one can substitute out a
deleterious residue in favor of any other residue, such as a
preferred residue as defined in Table IV; substitute a
less-preferred residue with a preferred residue as defined in Table
IV; or substitute an originally-occurring preferred residue with
another preferred residue as defined in Table IV. Substitutions can
occur at primary anchor positions or at other positions in a
peptide; see, e.g., Table IV.
[0192] A variety of references reflect the art regarding the
identification and generation of epitopes in a protein of interest
as well as analogs thereof. See, for example, WO 97/33602 to
Chesnut et al.; Sette, Immunogenetics 1999 50(34): 201-212; Sette
et al., J. Immunol. 2001 166(2): 1389-1397; Sidney et al., Hum.
Immunol. 1997 58(1): 12-20; Kondo et al., Immunogenetics 1997
45(4): 249-258; Sidney et al., J. Immunol. 1996 157(8): 3480-90;
and Falk et al., Nature 351: 290-6 (1991); Hunt et al., Science
255:1261-3 (1992); Parker et al., J. Immunol. 149:3580-7 (1992);
Parker et al., J. Immunol. 152:163-75 (1994)) Kast et al., 1994
152(8): 3904-12; Borras-Cuesta et al., Hum. Immunol. 2000 61(3):
266-278; Alexander et al., J. Immnunol. 2000 164(3); 164(3):
1625-1633; Alexander et al., PMID: 7895164, UI: 95202582;
O'Sullivan et al., J. Immunol. 1991 147(8): 2663-2669; Alexander et
al, Immunity 1994 1(9): 751-761 and Alexander et al., Immunol. Res.
1998 18(2): 79-92.
[0193] Related embodiments of the invention include polypeptides
comprising combinations of the different motifs set forth in Table
XX, and/or, one or more of the predicted CTL epitopes of Tables
V-XVII and XXII-XLVII, and/or, one or more of the predicted HTL
epitopes of Tables XLVIII-LI, and/or, one or more of the T cell
binding motifs known in the art. Preferred embodiments contain no
insertions, deletions or substitutions either within the motifs or
the intervening sequences of the polypeptides. In addition,
embodiments which include a number of either N-terminal and/or
C-terminal amino acid residues on either side of these motifs may
be desirable (to, for example, include a greater portion of the
polypeptide architecture in which the motif is located). Typically
the number of N-terminal and/or C-terminal amino acid residues on
either side of a motif is between about 1 to about 100 amino acid
residues, preferably 5 to about 50 amino acid residues.
[0194] 151P3D4-related proteins are embodied in many forms,
preferably in isolated form. A purified 151P3D4 protein molecule
will be substantially free of other proteins or molecules that
impair the binding of 151P3D4 to antibody, T cell or other ligand.
The nature and degree of isolation and purification will depend on
the intended use. Embodiments of a 151P3D4-related proteins include
purified 151P3D4-related proteins and functional, soluble
151P3D4-related proteins. In one embodiment, a functional, soluble
151P3D4 protein or fragment thereof retains the ability to be bound
by antibody, T cell or other ligand.
[0195] The invention also provides 151P3D4 proteins comprising
biologically active fragments of a 151P3D4 amino acid sequence
shown in FIG. 2 or FIG. 3. Such proteins exhibit properties of the
starting 151P3D4 protein, such as the ability to elicit the
generation of antibodies that specifically bind an epitope
associated with the starting 151P3D4 protein; to be bound by such
antibodies; to elicit the activation of HTL or CTL; and/or, to be
recognized by HTL or CTL that also specifically bind to the
starting protein. 15P3D4-related polypeptides that contain
particularly interesting structures can be predicted and/or
identified using various analytical techniques well known in the
art, including, for example, the methods of Chou-Fasman,
Garnier-Robson, Kyte-Doolittle, Eisenberg, Karplus-Schultz or
Jameson-Wolf analysis, or on the basis of immunogenicity. Fragments
that contain such structures are particularly useful in generating
subunit-specific anti-151P3D4 antibodies, or T cells or in
identifying cellular factors that bind to 151P3D4. For example,
hydrophilicity profiles can be generated, and immunogenic peptide
fragments identified, using the method of Hopp, T. P. and Woods, K.
R., 1981, Proc. Natl. Acad. Sci. U.S.A. 78:3824-3828.
Hydropathicity profiles can be generated, and immunogenic peptide
fragments identified, using the method of Kyte, J. and Doolittle,
R. F., 1982, J. Mol. Biol. 157:105-132. Percent (%) Accessible
Residues profiles can be generated, and immunogenic peptide
fragments identified, using the method of Janin J., 1979, Nature
277:491-492. Average Flexibility profiles can be generated, and
immunogenic peptide fragments identified, using the method of
Bhaskaran R., Ponnuswamy P. K., 1988, Int. J. Pept. Protein Res.
32:242-255. Beta-turn profiles can be generated, and immunogenic
peptide fragments identified, using the method of Deleage, G., Roux
B., 1987, Protein Engineering 1:289-294.
[0196] CTL epitopes can be determined using specific algorithms to
identify peptides within a 151P3D4 protein that are capable of
optimally binding to specified HLA alleles (e.g., by using the
SYFPEITHI site at World Wide Web URL syfpeithi.bmi-heidelberg.com/;
the listings in Table IV(A)-(E); Epimatrix.TM. and Epimer.TM.,
Brown University, URL
(www.brown.edu/Research/TB-HIV_Lab/epimatrix/epimatrix.html); and
BIMAS, URL bimas.dcrt.nih.gov/). Illustrating this, peptide
epitopes from 151P3D4 that are presented in the context of human
MHC Class I molecules, e.g., HLA-A1, A2, A3, A11, A24, B7 and B35
were predicted (see, e.g., Tables V-XVIII, XXII-LI). Specifically,
the complete amino acid sequence of the 151P3D4 protein and
relevant portions of other variants, i.e., for HLA Class I
predictions 9 flanking residues on either side of a point mutation,
and for HLA Class II predictions 14 flanking residues on either
side of a point mutation, were entered into the HLA Peptide Motif
Search algorithm found in the Bioinformatics and Molecular Analysis
Section (BIMAS) web site listed above; in addition to the site
SYFPEITHI, at URL syfpeithi.bmi-heidelberg.com/.
[0197] The HLA peptide motif search algorithm was developed by Dr.
Ken Parker based on binding of specific peptide sequences in the
groove of HLA Class I molecules, in particular HLA-A2 (see, e.g.,
Falk et al., Nature 351: 290-6 (1991); Hunt et al., Science
255:1261-3 (1992); Parker et al., J. Immunol. 149:3580-7 (1992);
Parker et al., J. Immunol. 152:163-75 (1994)). This algorithm
allows location and ranking of 8-mer, 9-mer, and 10-mer peptides
from a complete protein sequence for predicted binding to HLA-A2 as
well as numerous other HLA Class I molecules. Many HLA class I
binding peptides are 8-, 9-, 10 or 11-mers. For example, for Class
I HLA-A2, the epitopes preferably contain a leucine (L) or
methionine (M) at position 2 and a valine (V) or leucine (L) at the
C-terminus (see, e.g., Parker et al., J. Immunol. 149:3580-7
(1992)). Selected results of 151P3D4 predicted binding peptides are
shown in Tables V-XVIII and XXII-LI herein. In Tables V-XVIII and
XXII-XLVII, selected candidates, 9-mers and 10-mers, for each
family member are shown along with their location, the amino acid
sequence of each specific peptide, and an estimated binding score.
In Tables XLVIII-LI, selected candidates, 15-mers, for each family
member are shown along with their location, the amino acid sequence
of each specific peptide, and an estimated binding score. The
binding score corresponds to the estimated half time of
dissociation of complexes containing the peptide at 37.degree. C.
at pH 6.5. Peptides with the highest binding score are predicted to
be the most tightly bound to HLA Class I on the cell surface for
the greatest period of time and thus represent the best immunogenic
targets for T-cell recognition.
[0198] Actual binding of peptides to an HLA allele can be evaluated
by stabilization of HLA expression on the antigen-processing
defective cell line T2 (see, e.g., Xue et al., Prostate 30:73-8
(1997) and Peshwa et al., Prostate 36:129-38 (1998)).
Immunogenicity of specific peptides can be evaluated in vitro by
stimulation of CD8+ cytotoxic T lymphocytes (CTL) in the presence
of antigen presenting cells such as dendritic cells.
[0199] It is to be appreciated that every epitope predicted by the
BIMAS site, Epimer.TM. and Epimatrix.TM. sites, or specified by the
HLA class I or class II motifs available in the art or which become
part of the art such as set forth in Table IV (or determined using
World Wide Web site URL syfpeithi.bmi-heidelberg.com/, or BIMAS,
bimas.dcrt.nih.gov/) are to be "applied" to a 151P3D4 protein in
accordance with the invention. As used in this context "applied"
means that a 151P3D4 protein is evaluated, e.g., visually or by
computer-based patterns finding methods, as appreciated by those of
skill in the relevant art. Every subsequence of a 151P3D4 protein
of 8, 9, 10, or 11 amino acid residues that bears an HLA Class I
motif, or a subsequence of 9 or more amino acid residues that bear
an HLA Class II motif are within the scope of the invention.
[0200] III.B.) Expression of 151P3D4-Related Proteins
[0201] In an embodiment described in the examples that follow,
151P3D4 can be conveniently expressed in cells (such as 293T cells)
transfected with a conmmercially available expression vector such
as a CMV-driven expression vector encoding 151P3D4 with a
C-terminal 6XHis and MYC tag (pcDNA3.1/mycHIS, Invitrogen or TagS,
GenHunter Corporation, Nashville Tenn.). The TagS vector provides
an IgGK secretion signal that can be used to facilitate the
production of a secreted 151P3D4 protein in transfected cells. The
secreted HIS-tagged 151P3D4 in the culture media can be purified,
e.g., using a nickel column using standard techniques.
[0202] III.C.) Modifications of 151P3D4-Related Proteins
[0203] Modifications of 151P3D4-related proteins such as covalent
modifications are included within the scope of this invention. One
type of covalent modification includes reacting targeted amino acid
residues of a 151P3D4 polypeptide with an organic derivatizing
agent that is capable of reacting with selected side chains or the
N- or C-terminal residues of a 151P3D4 protein. Another type of
covalent modification of a 151P3D4 polypeptide included within the
scope of this invention comprises altering the native glycosylation
pattern of a protein of the invention. Another type of covalent
modification of 151P3D4 comprises linking a 151P3D4 polypeptide to
one of a variety of nonproteinaceous polymers, e.g., polyethylene
glycol (PEG), polypropylene glycol, or polyoxyalkylenes, in the
manner set forth in U.S. Pat. Nos. 4,640,835; 4,496,689; 4,301,144;
4,670,417; 4,791,192 or 4,179,337.
[0204] The 151P3D4-related proteins of the present invention can
also be modified to form a chimeric molecule comprising 151P3D4
fused to another, heterologous polypeptide or amino acid sequence.
Such a chimeric molecule can be synthesized chemically or
recombinantly. A chimeric molecule can have a protein of the
invention fused to another tumor-associated antigen or fragment
thereof. Alternatively, a protein in accordance with the invention
can comprise a fusion of fragments of a 151P3D4 sequence (amino or
nucleic acid) such that a molecule is created that is not, through
its length, directly homologous to the amino or nucleic acid
sequences shown in FIG. 2 or FIG. 3. Such a chimeric molecule can
comprise multiples of the same subsequence of 151P3D4. A chimeric
molecule can comprise a fusion of a 151P3D4-related protein with a
polyhistidine epitope tag, which provides an epitope to which
immobilized nickel can selectively bind, with cytokines or with
growth factors. The epitope tag is generally placed at the amino-
or carboxyl-terminus of a 151P3D4 protein. In an alternative
embodiment, the chimeric molecule can comprise a fusion of a
151P3D4-related protein with an immunoglobulin or a particular
region of an immunoglobulin. For a bivalent form of the chimeric
molecule (also referred to as an "immunoadhesin"), such a fusion
could be to the Fc region of an IgG molecule. The Ig fusions
preferably include the substitution of a soluble (transmembrane
domain deleted or inactivated) form of a 151P3D4 polypeptide in
place of at least one variable region within an Ig molecule. In a
preferred embodiment, the immunoglobulin fusion includes the hinge,
CH2 and CH3, or the hinge, CHI, CH2 and CH3 regions of an IgGI
molecule. For the production of immunoglobulin fusions see, e.g.,
U.S. Pat. No. 5,428,130 issued Jun. b 27, 1995.
[0205] III.D.) Uses of 151P3D4-Related Proteins
[0206] The proteins of the invention have a number of different
specific uses. As 151P3D4 is highly expressed in prostate and other
cancers, 151P3D4-related proteins are used in methods that assess
the status of 151P3D4 gene products in normal versus cancerous
tissues, thereby elucidating the malignant phenotype. Typically,
polypeptides from specific regions of a 151P3D4 protein are used to
assess the presence of perturbations (such as deletions,
insertions, point mutations etc.) in those regions (such as regions
containing one or more motifs). Exemplary assays utilize antibodies
or T cells targeting 151P3D4-related proteins comprising the amino
acid residues of one or more of the biological motifs contained
within a 151P3D4 polypeptide sequence in order to evaluate the
characteristics of this region in normal versus cancerous tissues
or to elicit an immune response to the epitope. Alternatively,
151P3D4-related proteins that contain the amino acid residues of
one or more of the biological motifs in a 151P3D4 protein are used
to screen for factors that interact with that region of
151P3D4.
[0207] 151P3D4 protein fragments/subsequences are particularly
useful in generating and characterizing domain-specific antibodies
(e.g., antibodies recognizing an extracellular or intracellular
epitope of a 151P3D4 protein), for identifying agents or cellular
factors that bind to 151P3D4 or a particular structural domain
thereof, and in various therapeutic and diagnostic contexts,
including but not limited to diagnostic assays, cancer vaccines and
methods of preparing such vaccines.
[0208] Proteins encoded by the 151P3D4 genes, or by analogs,
homologs or fragments thereof, have a variety of uses, including
but not limited to generating antibodies and in methods for
identifying ligands and other agents and cellular constituents that
bind to a 151P3D4 gene product. Antibodies raised against a 151P3D4
protein or fragment thereof are useful in diagnostic and prognostic
assays, and imaging methodologies in the management of human
cancers characterized by expression of 151P3D4 protein, such as
those listed in Table I. Such antibodies can be expressed
intracellularly and used in methods of treating patients with such
cancers. 151P3D4-related nucleic acids or proteins are also used in
generating HTL or CTL responses.
[0209] Various immunological assays useful for the detection of
151P3D4 proteins are used, including but not limited to various
types of radioimmunoassays, enzyme-linked immunosorbent assays
(ELISA), enzyme-linked immunofluorescent assays (ELIFA),
immunocytochemical methods, and the like. Antibodies can be labeled
and used as immunological imaging reagents capable of detecting
151P3D4-expressing cells (e.g., in radioscintigraphic imaging
methods). 151P3D4 proteins are also particularly useful in
generating cancer vaccines, as further described herein.
[0210] IV.) 151P3D4 Antibodies
[0211] Another aspect of the invention provides antibodies that
bind to 151P3D4-related proteins. Preferred antibodies specifically
bind to a 151P3D4-related protein and do not bind (or bind weakly)
to peptides or proteins that are not 151P3D4-related proteins. For
example, antibodies that bind 151P3D4 can bind 151P3D4-related
proteins such as the homologs or analogs thereof.
[0212] 151P3D4 antibodies of the invention are particularly useful
in cancer (see, e.g., Table I) diagnostic and prognostic assays,
and imaging methodologies. Similarly, such antibodies are useful in
the treatment, diagnosis, and/or prognosis of other cancers, to the
extent 151P3D4 is also expressed or overexpressed in these other
cancers. Moreover, intracellularly expressed antibodies (e.g.,
single chain antibodies) are therapeutically useful in treating
cancers in which the expression of 151P3D4 is involved, such as
advanced or metastatic prostate cancers.
[0213] The invention also provides various immunological assays
useful for the detection and quantification of 151P3D4 and mutant
151P3D4-related proteins. Such assays can comprise one or more
151P3D4 antibodies capable of recognizing and binding a
151P3D4-related protein, as appropriate. These assays are performed
within various immunological assay formats well known in the art,
including but not limited to various types of radioimmunoassay,
enzyme-linked immunosorbent assays (ELISA), enzyme-linked
immunofluorescent assays (ELIFA), and the like.
[0214] Immunological non-antibody assays of the invention also
comprise T cell immunogenicity assays (inhibitory or stimulatory)
as well as major histocompatibility complex (MHC) binding
assays.
[0215] In addition, immunological imaging methods capable of
detecting prostate cancer and other cancers expressing 151P3D4 are
also provided by the invention, including but not limited to
radioscintigraphic imaging methods using labeled 151P3D4
antibodies. Such assays are clinically useful in the detection,
monitoring, and prognosis of 151P3D4 expressing cancers such as
prostate cancer. 151P3D4 antibodies are also used in methods for
purifying a 151P3D4-related protein and for isolating 151P3D4
homologues and related molecules. For example, a method of
purifying a 151P3D4-related protein comprises incubating a 151P3D4
antibody, which has been coupled to a solid matrix, with a lysate
or other solution containing a 151P3D4-related protein under
conditions that permit the 151P3D4 antibody to bind to
151P3D4-related protein; washing the solid matrix to eliminate
impurities; and eluting the 151P3D4-related protein from the
coupled antibody. Other uses of 151P3D4 antibodies in accordance
with the invention include generating anti-idiotypic antibodies
that mimic a 151P3D4 protein.
[0216] Various methods for the preparation of antibodies are well
known in the art. For example, antibodies can be prepared by
immunizing a suitable mammalian host using a 151P3D4-related
protein, peptide, or fragment, in isolated or immunoconjugated form
(Antibodies: A Laboratory Manual, CSH Press, Eds., Harlow, and Lane
(1988); Harlow, Antibodies, Cold Spring Harbor Press, NY (1989)).
In addition, fusion proteins of 151P3D4 can also be used, such as a
151P3D4 GST-fusion protein. In a particular embodiment, a GST
fusion protein comprising all or most of the amino acid sequence of
FIG. 2 or FIG. 3 is produced, then used as an immunogen to generate
appropriate antibodies. In another embodiment, a 151P3D4-related
protein is synthesized and used as an immunogen.
[0217] In addition, naked DNA immunization techniques known in the
art are used (with or without purified 151P3D4-related protein or
151P3D4 expressing cells) to generate an immune response to the
encoded immunogen (for review, see Donnelly et al., 1997, Ann. Rev.
Immunol. 15: 617-648).
[0218] The amino acid sequence of a 151P3D4 protein as shown in
FIG. 2 or FIG. 3 can be analyzed to select specific regions of the
151P3D4 protein for generating antibodies. For example,
hydrophobicity and hydrophilicity analyses of a 151P3D4 amino acid
sequence are used to identify hydrophilic regions in the 151P3D4
structure. Regions of a 151P3D4 protein that show immunogenic
structure, as well as other region domains, can readily be
identified using various other methods known in the art, such as
Chou-Fasman, Garnier-Robson, Kyte-Doolittle, Eisenberg,
Karplus-Schultz or Jameson-Wolf analysis. Hydrophilicity profiles
can be generated using the method of Hopp, T. P. and Woods, K. R.,
1981, Proc. Natl. Acad. Sci. U.S.A. 78:3824-3828. Hydropathicity
profiles can be generated using the method of Kyte, J. and
Doolittle, R. F., 1982, J. Mol. Biol. 157:105-132. Percent (%)
Accessible Residues profiles can be generated using the method of
Janin J., 1979, Nature 277:491-492. Average Flexibility profiles
can be generated using the method of Bhaskaran R., Ponnuswamy P.
K., 1988, Int. J. Pept. Protein Res. 32:242-255. Beta-turn profiles
can be generated using the method of Deleage, G., Roux B., 1987,
Protein Engineering 1:289-294. Thus, each region identified by any
of these programs or methods is within the scope of the present
invention. Methods for the generation of 151P3D4 antibodies are
further illustrated by way of the examples provided herein. Methods
for preparing a protein or polypeptide for use as an immunogen are
well known in the art. Also well known in the art are methods for
preparing immunogenic conjugates of a protein with a carrier, such
as BSA, KLH or other carrier protein. In some circumstances, direct
conjugation using, for example, carbodiimide reagents are used; in
other instances linking reagents such as those supplied by Pierce
Chemical Co., Rockford, Ill., are effective. Administration of a
151P3D4 immunogen is often conducted by injection over a suitable
time period and with use of a suitable adjuvant, as is understood
in the art. During the immunization schedule, titers of antibodies
can be taken to determine adequacy of antibody formation.
[0219] 151P3D4 monoclonal antibodies can be produced by various
means well known in the art. For example, immortalized cell lines
that secrete a desired monoclonal antibody are prepared using the
standard hybridoma technology of Kohler and Milstein or
modifications that immortalize antibody-producing B cells, as is
generally known. Immortalized cell lines that secrete the desired
antibodies are screened by immunoassay in which the antigen is a
151P3D4-related protein. When the appropriate immortalized cell
culture is identified, the cells can be expanded and antibodies
produced either from in vitro cultures or from ascites fluid.
[0220] The antibodies or fragments of the invention can also be
produced, by recombinant means. Regions that bind specifically to
the desired regions of a 151P3D4 protein can also be produced in
the context of chimeric or complementarity determining region (CDR)
grafted antibodies of multiple species origin. Humanized or human
151P3D4 antibodies can also be produced, and are preferred for use
in therapeutic contexts. Methods for humanizing murine and other
non-human antibodies, by substituting one or more of the non-human
antibody CDRs for corresponding human antibody sequences, are well
known (see for example, Jones et al., 1986, Nature 321: 522-525;
Riechann et al., 1988, Nature332: 323-327; Verhoeyen et al., 1988,
Science 239: 1534-1536). See also, Carter et al., 1993, Proc. Natl.
Acad. Sci. USA 89: 4285 and Sims et al., 1993, J. Immunol. 151:
2296.
[0221] Methods for producing fully human monoclonal antibodies
include phage display and transgenic methods (for review, see
Vaughan et a., 1998, Nature Biotechnology 16: 535-539). Fully human
151P3D4 monoclonal antibodies can be generated using cloning
technologies employing large human Ig gene combinatorial libraries
(i.e., phage display) (Griffiths and Hoogenboom, Building an in
vitro immune system: human antibodies from phage display libraries.
In: Protein Engineering of Antibody Molecules for Prophylactic and
Therapeutic Applications in Man, Clark, M. (Ed.), Nottingham
Academic, pp 45-64 (1993); Burton and Barbas, Human Antibodies from
combinatorial libraries. Id., pp 65-82). Fully human 151P3D4
monoclonal antibodies can also be produced using transgenic mice
engineered to contain human immunoglobulin gene loci as described
in PCT Patent Application WO98/24893, Kucherlapati and Jakobovits
et al., published Dec. 3, 1997 (see also, Jakobovits, 1998, Exp.
Opin. Invest. Drugs 7(4): 607-614; U.S. Pat. Nos. 6,162,963 issued
Dec. 19, 2000; 6,150,584 issued Nov. 12, 2000; and, 6,114598 issued
Sep. 5, 2000). This method avoids the in vitro manipulation
required with phage display technology and efficiently produces
high affinity authentic human antibodies.
[0222] Reactivity of 151P3D4 antibodies with a 151P3D4-related
protein can be established by a number of well known means,
including Western blot, immunoprecipitation, ELISA, and FACS
analyses using, as appropriate, 151P3D4-related proteins,
151P3D4-expressing cells or extracts thereof. A 151P3D4 antibody or
fragment thereof can be labeled with a detectable marker or
conjugated to a second molecule. Suitable detectable markers
include, but are not limited to, a radioisotope, a fluorescent
compound, a bioluminescent compound, chemiluminescent compound, a
metal chelator or an enzyme. Further, bi-specific antibodies
specific for two or more 151P3D4 epitopes are generated using
methods generally known in the art. Homodimeric antibodies can also
be generated by cross-linking techniques known in the art (e.g.,
Wolff et al., Cancer Res. 53: 2560-2565).
[0223] V.) 151P3D4 Cellular Immune Responses
[0224] The mechanism by which T cells recognize antigens has been
delineated. Efficacious peptide epitope vaccine compositions of the
invention induce a therapeutic or prophylactic immune responses in
very broad segments of the world-wide population. For an
understanding of the value and efficacy of compositions of the
invention that induce cellular immune responses, a brief review of
immunology-related technology is provided.
[0225] A complex of an HLA molecule and a peptidic antigen acts as
the ligand recognized by HLA-restricted T cells (Buus, S. et al.,
Cell 47:1071, 1986; Babbitt, B. P. et al., Nature 317:359, 1985;
Townsend, A. and Bodmer, H., Annu. Rev. Immunol. 7:601, 1989;
Germain, R. N., Annu. Rev. Immunol. 11:403, 1993). Through the
study of single amino acid substituted antigen analogs and the
sequencing of endogenously bound, naturally processed peptides,
critical residues that correspond to motifs required for specific
binding to HLA antigen molecules have been identified and are set
forth in Table IV (see also, e.g., Southwood, et al., J. Immunol.
160:3363, 1998; Rammensee, et al., Immunogenetics 41:178, 1995;
Rammensee et al., SYFPEITHI, access via World Wide Web at URL
syfpeithi.bmi-heidelberg.com/; Sette, A. and Sidney, J. Curr. Opin.
Immunol. 10:478, 1998; Engelhard, V. H.,Curr. Opin. Immunol. 6:13,
1994; Sette, A. and Grey, H. M., Curr. Opin. Immunol. 4:79, 1992;
Sinigaglia, F. and Hammer, J. Curr. Biol. 6:52, 1994; Ruppert et
al., Cell 74:929-937, 1993; Kondo et al., J. Immunol.
155:4307-4312, 1995; Sidney et al., J. Immunol. 157:3480-3490,
1996; Sidney et al., Human Immunol. 45:79-93, 1996; Sette, A. and
Sidney, J. Immunogenetics November 1999; 50(3-4):201-12,
Review).
[0226] Furthermore, x-ray crystallographic analyses of HLA-peptide
complexes have revealed pockets within the peptide binding
cleft/groove of HLA molecules which accommodate, in an
allele-specific mode, residues borne by peptide ligands; these
residues in turn determine the HLA binding capacity of the peptides
in which they are present. (See, e.g., Madden, D. R. Annu. Rev.
Immunol. 13:587, 1995; Smith, et al., Immunity 4:203, 1996; Fremont
et al., Immunity 8:305, 1998; Stern et al., Structure 2:245, 1994;
Jones, E. Y. Curr. Opin. Immunol. 9:75, 1997; Brown, J. H. et al.,
Nature 364:33, 1993; Guo, H. C. et al., Proc. Natl. Acad. Sci. USA
90:8053, 1993; Guo, H. C. et al., Nature 360:364, 1992; Silver, M.
L. et al., Nature 360:367, 1992; Matsumura, M. et al., Science
257:927, 1992; Madden et al., Cell 70:1035, 1992; Fremont, D. H. et
al., Science 257:919, 1992; Saper, M. A., Bjorkman, P. J. and
Wiley, D. C., J. Mol. Biol. 219:277, 1991.)
[0227] Accordingly, the definition of class I and class II
allele-specific HLA binding motifs, or class I or class II
supermotifs allows identification of regions within a protein that
are correlated with binding to particular HLA antigen(s).
[0228] Thus, by a process of HLA motif identification, candidates
for epitope-based vaccines have been identified; such candidates
can be further evaluated by HLA-peptide binding assays to determine
binding affinity and/or the time period of association of the
epitope and its corresponding HLA molecule. Additional confirmatory
work can be performed to select, amongst these vaccine candidates,
epitopes with preferred characteristics in terms of population
coverage, and/or immunogenicity.
[0229] Various strategies can be utilized to evaluate cellular
immunogenicity, including:
[0230] 1) Evaluation of primary T cell cultures from normal
individuals (see, e.g., Wentworth, P. A. et al., Mol. Immunol.
32:603, 1995; Celis, E. et al., Proc. Natl. Acad. Sci. USA 91:2105,
1994; Tsai, V. et al., J. Immunol. 158:1796, 1997; Kawashima, I. et
al., Human Immunol. 59:1, 1998). This procedure involves the
stimulation of peripheral blood lymphocytes (PBL) from normal
subjects with a test peptide in the presence of antigen presenting
cells in vitro over a period of several weeks. T cells specific for
the peptide become activated during this time and are detected
using, e.g., a lymphokine- or .sup.51Cr-release assay involving
peptide sensitized target cells.
[0231] 2) Immunization of HLA transgenic mice (see, e.g.,
Wentworth, P. A. et al., J. Immunol. 26:97, 1996; Wentworth, P. A.
et al., Int. Immunol. 8:651, 1996; Alexander, J. et al., J.
Immunol. 159:4753, 1997). For example, in such methods peptides in
incomplete Freund's adjuvant are administered subcutaneously to HLA
transgenic mice. Several weeks following immunization, splenocytes
are removed and cultured in vitro in the presence of test peptide
for approximately one week. Peptide-specific T cells are detected
using, e.g., a .sup.51Cr-release assay involving peptide sensitized
target cells and target cells expressing endogenously generated
antigen.
[0232] 3) Demonstration of recall T cell responses from immune
individuals who have been either effectively vaccinated and/or from
chronically ill patients (see, e.g., Rehermann, B. et al., J. Exp.
Med. 181:1047, 1995; Doolan, D. L. et al., Immunity 7:97, 1997;
Bertoni, R. et al., J. Clin. Invest. 100:503, 1997; Threlkeld, S.
C. et al., J. Immunol. 159:1648, 1997; Diepolder, H. M. et al., J.
Virol. 71:6011, 1997). Accordingly, recall responses are detected
by culturing PBL from subjects that have been exposed to the
antigen due to disease and thus have generated an immune response
"naturally", or from patients who were vaccinated against the
antigen. PBL from subjects are cultured in vitro for 1-2 weeks in
the presence of test peptide plus antigen presenting cells (APC) to
allow activation of "memory" T cells, as compared to "naive" T
cells. At the end of the culture period, T cell activity is
detected using assays including .sup.51Cr release involving
peptide-sensitized targets, T cell proliferation, or lymphokine
release.
[0233] VI.) 151P3D4 Transzenic Animals
[0234] Nucleic acids that encode a 151P3D4-related protein can also
be used to generate either transgenic animals or "knock out"
animals that, in turn, are useful in the development and screening
of therapeutically useful reagents. In accordance with established
techniques, cDNA encoding 151P3D4 can be used to clone genomic DNA
that encodes 151P3D4. The cloned genomic sequences can then be used
to generate transgenic animals containing cells that express DNA
that encode 151P3D4. Methods for generating transgenic animals,
particularly animals such as mice or rats, have become conventional
in the art and are described, for example, in U.S. Pat. Nos.
4,736,866 issued Apr. 12, 1988, and 4,870,009 issued Sep. 26, 1989.
Typically, particular cells would be targeted for 151P3D4 transgene
incorporation with tissue-specific enhancers.
[0235] Transgenic animals that include a copy of a transgene
encoding 151P3D4 can be used to examine the effect of increased
expression of DNA that encodes 151P3D4. Such animals can be used as
tester animals for reagents thought to confer protection from, for
example, pathological conditions associated with its
overexpression. In accordance with this aspect of the invention, an
animal is treated with a reagent and a reduced incidence of a
pathological condition, compared to untreated animals that bear the
transgene, would indicate a potential therapeutic intervention for
the pathological condition.
[0236] Alternatively, non-human homologues of 151P3D4 can be used
to construct a 151P3D4 "knock out" animal that has a defective or
altered gene encoding 151P3D4 as a result of homologous
recombination between the endogenous gene encoding 151P3D4 and
altered genomic DNA encoding 151P3D4 introduced into an embryonic
cell of the animal. For example, cDNA that encodes 151P3D4 can be
used to clone genomic DNA encoding 151P3D4 in accordance with
established techniques. A portion of the genomic DNA encoding
151P3D4 can be deleted or replaced with another gene, such as a
gene encoding a selectable marker that can be used to monitor
integration. Typically, several kilobases of unaltered flanking DNA
(both at the 5' and 3' ends) are included in the vector (see, e.g.,
Thomas and Capecchi, Cell 51:503 (1987) for a description of
homologous recombination vectors). The vector is introduced into an
embryonic stem cell line (e.g., by electroporation) and cells in
which the introduced DNA has homologously recombined with the
endogenous DNA are selected (see, e.g., Li et al., Cell, 69:915
(1992)). The selected cells are then injected into a blastocyst of
an animal (e.g., a mouse or rat) to form aggregation chimeras (see,
e.g., Bradley, in Teratocarcinomas and Embryonic Stem Cells: A
Practical Approach, E. J. Robertson, ed. (IRL, Oxford, 1987), pp.
113-152). A chimeric embryo can then be implanted into a suitable
pseudopregnant female foster animal, and the embryo brought to term
to create a "knock out" animal. Progeny harboring the homologously
recombined DNA in their germ cells can be identified by standard
techniques and used to breed animals in which all cells of the
animal contain the homologously recombined DNA. Knock out animals
can be characterized, for example, for their ability to defend
against certain pathological conditions or for their development of
pathological conditions due to absence of a 151P3D4
polypeptide.
[0237] VII.) Methods for the Detection of 151P3D4
[0238] Another aspect of the present invention relates to methods
for detecting 151P3D4 polynucleotides and 151P3D4-related proteins,
as well as methods for identifying a cell that expresses 151P3D4.
The expression profile of 151P3D4 makes it a diagnostic marker for
metastasized disease. Accordingly, the status of 151P3D4 gene
products provides information useful for predicting a variety of
factors including susceptibility to advanced stage disease, rate of
progression, and/or tumor aggressiveness. As discussed in detail
herein, the status of 151P3D4 gene products in patient samples can
be analyzed by a variety protocols that are well known in the art
including immunohistochemical analysis, the variety of Northern
blotting techniques including in situ hybridization, RT-PCR
analysis (for example on laser capture micro-dissected samples),
Western blot analysis and tissue array analysis.
[0239] More particularly, the invention provides assays for the
detection of 151P3D4 polynucleotides in a biological sample, such
as serum, bone, prostate, and other tissues, urine, semen, cell
preparations, and the like. Detectable 151P3D4 polynucleotides
include, for example, a 151P3D4 gene or fragment thereof, 151P3D4
mRNA, alternative splice variant 151P3D4 mRNAs, and recombinant DNA
or RNA molecules that contain a 151P3D4 polynucleotide. A number of
methods for amplifying and/or detecting the presence of 151P3D4
polynucleotides are well known in the art and can be employed in
the practice of this aspect of the invention.
[0240] In one embodiment, a method for detecting a 151P3D4 mRNA in
a biological sample comprises producing cDNA from the sample by
reverse transcription using at least one primer; amplifying the
cDNA so produced using a 151P3D4 polynucleotides as sense and
antisense primers to amplify 151P3D4 cDNAs therein; and detecting
the presence of the amplified 151P3D4 cDNA. Optionally, the
sequence of the amplified 151P3D4 cDNA can be determined.
[0241] In another embodiment, a method of detecting a 151P3D4 gene
in a biological sample comprises first isolating genomic DNA from
the sample; amplifying the isolated genomic DNA using 151P3D4
polynucleotides as sense and antisense primers; and detecting the
presence of the amplified 151P3D4 gene. Any number of appropriate
sense and antisense probe combinations can be designed from a
151P3D4 nucleotide sequence (see, e.g., FIG. 2) and used for this
purpose.
[0242] The invention also provides assays for detecting the
presence of a 151P3D4 protein in a tissue or other biological
sample such as serum, semen, bone, prostate, urine, cell
preparations, and the like. Methods for detecting a 151P3D4-related
protein are also well known and include, for example,
immunoprecipitation, immunohistochemical analysis, Western blot
analysis, molecular binding assays, ELISA, ELIFA and the like. For
example, a method of detecting the presence of a 151P3D4-related
protein in a biological sample comprises first contacting the
sample with a 151P3D4 antibody, a 151P3D4-reactive fragment
thereof, or a recombinant protein containing an antigen binding
region of a 151P3D4 antibody; and then detecting the binding of
151P3D4-related protein in the sample.
[0243] Methods for identifying a cell that expresses 151P3D4 are
also within the scope of the invention. In one embodiment, an assay
for identifying a cell that expresses a 151P3D4 gene comprises
detecting the presence of 151P3D4 mRNA in the cell. Methods for the
detection of particular mRNAs in cells are well known and include,
for example, hybridization assays using complementary DNA probes
(such as in situ hybridization using labeled 151P3D4 riboprobes,
Northern blot and related techniques) and various nucleic acid
amplification assays (such as RT-PCR using complementary primers
specific for 151P3D4, and other amplification type detection
methods, such as, for example, branched DNA, SISBA, TMA and the
like). Alternatively, an assay for identifying a cell that
expresses a 151P3D4 gene comprises detecting the presence of
151P3D4-related protein in the cell or secreted by the cell.
Various methods for the detection of proteins are well known in the
art and are employed for the detection of 151P3D4-related proteins
and cells that express 151P3D4-related proteins.
[0244] 151P3D4 expression analysis is also useful as a tool for
identifying and evaluating agents that modulate 151P3D4 gene
expression. For example, 151P3D4 expression is significantly
upregulated in prostate cancer, and is expressed in cancers of the
tissues listed in Table I. Identification of a molecule or
biological agent that inhibits 151P3D4 expression or
over-expression in cancer cells is of therapeutic value. For
example, such an agent can be identified by using a screen that
quantifies 151P3D4 expression by RT-PCR, nucleic acid hybridization
or antibody binding.
[0245] VIII.) Methods for Monitoring the Status of 151P3D4-Related
Genes and Their Products
[0246] Oncogenesis is known to be a multistep process where
cellular growth becomes progressively dysregulated and cells
progress from a normal physiological state to precancerous and then
cancerous states (see, e.g., Alers et al., Lab Invest. 77(5):
437-438 (1997) and Isaacs et al., Cancer Surv. 23: 19-32 (1995). In
this context, examining a biological sample for evidence of
dysregulated cell growth (such as aberrant 151P3D4 expression in
cancers) allows for early detection of such aberrant physiology,
before a pathologic state such as cancer has progressed to a stage
that therapeutic options are more limited and or the prognosis is
worse. In such examinations, the status of 151P3D4 in a biological
sample of interest can be compared, for example, to the status of
151P3D4 in a corresponding normal sample (e.g. a sample from that
individual or alternatively another individual that is not affected
by a pathology). An alteration in the status of 151P3D4 in the
biological sample (as compared to the normal sample) provides
evidence of dysregulated cellular growth. In addition to using a
biological sample that is not affected by a pathology as a normal
sample, one can also use a predetermined normative value such as a
predetermined normal level of mRNA expression (see, e.g., Grever et
al., J. Comp. Neurol. Dec. 9, 1996; 376(2): 306-14 and U.S. Pat.
No. 5,837,501) to compare 151P3D4 status in a sample.
[0247] The term "status" in this context is used according to its
art accepted meaning and refers to the condition or state of a gene
and its products. Typically, skilled artisans use a number of
parameters to evaluate the condition or state of a gene and its
products. These include, but are not limited to the location of
expressed gene products (including the location of 151P3D4
expressing cells) as well as the level, and biological activity of
expressed gene products (such as 151P3D4 mRNA, polynucleotides and
polypeptides). Typically, an alteration in the status of 151P3D4
comprises a change in the location of 151P3D4 and/or 151P3D4
express increase in 151P3D4 mRNA and/or protein expression.
[0248] 151P3D4 status in a sample can be analyzed by a number of
means well known in the art, including without limitation,
immunohistochemical analysis, in situ hybridization, RT-PCR
analysis on laser capture micro-dissected samples, Western blot
analysis, and tissue array analysis. Typical protocols for
evaluating the status of a 151P3D4 gene and gene products are
found, for example in Ausubel et al. eds., 1995, Current Protocols
In Molecular Biology, Units 2 (Northern Blotting), 4 (Southern
Blotting), 15 (Immunoblotting) and 18 (PCR Analysis). Thus, the
status of 151P3D4 in a biological sample is evaluated by various
methods utilized by skilled artisans including, but not limited to
genomic Southern analysis (to examine, for example perturbations in
a 151P3D4 gene), Northern analysis and/or PCR analysis of 151P3D4
mRNA (to examine, for example alterations in the polynucleotide
sequences or expression levels of 151P3D4 mRNAs), and, Western
and/or immunohistochemical analysis (to examine, for example
alterations in polypeptide sequences, alterations in polypeptide
localization within a sample, alterations in expression levels of
151P3D4 proteins and/or associations of 151P3D4 proteins with
polypeptide binding partners). Detectable 151P3D4 polynucleotides
include, for example, a 151P3D4 gene or fragment thereof, 151P3D4
mRNA, alternative splice variants, 151P3D4 mRNAs, and recombinant
DNA or RNA molecules containing a 151P3D4 polynucleotide.
[0249] The expression profile of 151P3D4 makes it a diagnostic
marker for local and/or metastasized disease, and provides
information on the growth or oncogenic potential of a biological
sample. In particular, the status of 151P3D4 provides information
useful for predicting susceptibility to particular disease stages,
progression, and/or tumor aggressiveness. The invention provides
methods and assays for determining 151P3D4 status and diagnosing
cancers that express 151P3D4, such as cancers of the tissues listed
in Table I. For example, because 151P3D4 mRNA is so highly
expressed in prostate and other cancers relative to normal prostate
tissue, assays that evaluate the levels of 151P3D4 mRNA transcripts
or proteins in a biological sample can be used to diagnose a
disease associated with 151P3D4 dysregulation, and can provide
prognostic information useful in defining appropriate therapeutic
options.
[0250] The expression status of 151P3D4 provides information
including the presence, stage and location of dysplastic,
precancerous and cancerous cells, predicting susceptibility to
various stages of disease, and/or for gauging tumor aggressiveness.
Moreover, the expression profile makes it useful as an imaging
reagent for metastasized disease. Consequently, an aspect of the
invention is directed to the various molecular prognostic and
diagnostic methods for examining the status of 151P3D4 in
biological samples such as those from individuals suffering from,
or suspected of suffering from a pathology characterized by
dysregulated cellular growth, such as cancer.
[0251] As described above, the status of 151P3D4 in a biological
sample can be examined by a number of well-known procedures in the
art. For example, the status of 151P3D4 in a biological sample
taken from a specific location in the body can be examined by
evaluating the sample for the presence or absence of 151P3D4
expressing cells (e.g. those that express 151P3D4 mRNAs or
proteins). This examination can provide evidence of dysregulated
cellular growth, for example, when 151P3D4-expressing cells are
found in a biological sample that does not normally contain such
cells (such as a lymph node), because such alterations in the
status of 151P3D4 in a biological sample are often associated with
dysregulated cellular growth. Specifically, one indicator of
dysregulated cellular growth is the metastases of cancer cells from
an organ of origin (such as the prostate) to a different area of
the body (such as a lymph node). In this context, evidence of
dysregulated cellular growth is important for example because
occult lymph node metastases can be detected in a substantial
proportion of patients with prostate cancer, and such metastases
are associated with known predictors of disease progression (see,
e.g., Murphy et al., Prostate 42(4): 315-317 (2000);Su et al.,
Semin. Surg. Oncol. 18(1): 17-28 (2000) and Freeman et al., J Urol
August 1995 154(2 Pt 1):474-8).
[0252] In one aspect, the invention provides methods for monitoring
151P3D4 gene products by determining the status of 151P3D4 gene
products expressed by cells from an individual suspected of having
a disease associated with dysregulated cell growth (such as
hyperplasia or cancer) and then comparing the status so determined
to the status of 151P3D4 gene products in a corresponding normal
sample. The presence of aberrant 151P3D4 gene products in the test
sample relative to the normal sample provides an indication of the
presence of dysregulated cell growth within the cells of the
individual.
[0253] In another aspect, the invention provides assays useful in
determining the presence of cancer in an individual, comprising
detecting a significant increase in 151P3D4 mRNA or protein
expression in a test cell or tissue sample relative to expression
levels in the corresponding normal cell or tissue. The presence of
151P3D4 mRNA can, for example, be evaluated in tissues including
but not limited to those listed in Table I. The presence of
significant 151P3D4 expression in any of these tissues is useful to
indicate the emergence, presence and/or severity of a cancer, since
the corresponding normal tissues do not express 151P3D4 mRNA or
express it at lower levels.
[0254] In a related embodiment, 151P3D4 status is determined at the
protein level rather than at the nucleic acid level. For example,
such a method comprises determining the level of 151P3D4 protein
expressed by cells in a test tissue sample and comparing the level
so determined to the level of 151P3D4 expressed in a corresponding
normal sample. In one embodiment, the presence of 151P3D4 protein
is evaluated, for example, using immunohistochemical methods.
151P3D4 antibodies or binding partners capable of detecting 151P3D4
protein, expression are used in a variety of assay formats well
known in the art for this purpose.
[0255] In a further embodiment, one can evaluate the status of
151P3D4 nucleotide and amino acid sequences in a biological sample
in order to identify perturbations in the structure of these
molecules. These perturbations can include insertions, deletions,
substitutions and the like. Such evaluations are useful because
perturbations in the nucleotide and amino acid sequences are
observed in a large number of proteins associated with a growth
dysregulated phenotype (see, e.g., Marrogi et al., 1999, J. Cutan.
Pathol. 26(8):369-378). For example, a mutation in the sequence of
151P3D4 may be indicative of the presence or promotion of a tumor.
Such assays therefore have diagnostic and predictive value where a
mutation in 151P3D4 indicates a potential loss of function or
increase in tumor growth.
[0256] A wide variety of assays for observing perturbations in
nucleotide and amino acid sequences are well known in the art. For
example, the size and structure of nucleic acid or amino acid
sequences of 151P3D4 gene products are observed by the Northern,
Southern, Western, PCR and DNA sequencing protocols discussed
herein. In addition, other methods for observing perturbations in
nucleotide and amino acid sequences such as single strand
conformation polymorphism analysis are well known in the art (see,
e.g., U.S. Pat. Nos. 5,382,510 issued Sep. 7, 1999 and 5,952,170
issued Jan. 17, 1995).
[0257] Additionally, one can examine the methylation status of a
151P3D4 gene in a biological sample. Aberrant demethylation and/or
hypermethylation of CpG islands in gene 5' regulatory regions
frequently occurs in immortalized and transformed cells, and can
result in altered expression of various genes. For example,
promoter hypermethylation of the pi-class glutathione S-transferase
(a protein expressed in normal prostate but not expressed in
>90% of prostate carcinomas) appears to permanently silence
transcription of this gene and is the most frequently detected
genomic alteration in prostate carcinomas (De Marzo et al., Am. J.
Pathol. 155(6): 1985-1992 (1999)). In addition, this alteration is
present in at least 70% of cases of high-grade prostatic
intraepithelial neoplasia (PIN) (Brooks et al., Cancer Epidemiol.
Biomarkers Prev., 1998, 7:531-536). In another example, expression
of the LAGE-I tumor specific gene (which is not expressed in normal
prostate but is expressed in 25-50% of prostate cancers) is induced
by deoxy-azacytidine in lymphoblastoid cells, suggesting that
tumoral expression is due to demethylation (Lethe et al., Int. J.
Cancer 76(6): 903-908 (1998)). A variety of assays for examining
methylation status of a gene are well known in the art. For
example, one can utilize, in Southern hybridization approaches,
methylation-sensitive restriction enzymes that cannot cleave
sequences that contain methylated CpG sites to assess the
methylation status of CpG islands. In addition, MSP (methylation
specific PCR) can rapidly profile the methylation status of all the
CpG sites present in a CpG island of a given gene. This procedure
involves initial modification of DNA by sodium bisulfite (which
will convert all unmethylated cytosines to uracil) followed by
amplification using primers specific for methylated versus
unmethylated DNA. Protocols involving methylation interference can
also be found for example in Current Protocols In Molecular
Biology, Unit 12, Frederick M. Ausubel et al. eds., 1995.
[0258] Gene amplification is an additional method for assessing the
status of 151P3D4. Gene amplification is measured in a sample
directly, for example, by conventional Southern blotting or
Northern blotting to quantitate the transcription of mRNA (Thomas,
1980, Proc. Natl. Acad. Sci. USA, 77:5201-5205), dot blotting (DNA
analysis), or in situ hybridization, using an appropriately labeled
probe, based on the sequences provided herein. Alternatively,
antibodies are employed that recognize specific duplexes, including
DNA duplexes, RNA duplexes, and DNA-RNA hybrid duplexes or
DNA-protein duplexes. The antibodies in turn are labeled and the
assay carried out where the duplex is bound to a surface, so that
upon the formation of duplex on the surface, the presence of
antibody bound to the duplex can be detected.
[0259] Biopsied tissue or peripheral blood can be conveniently
assayed for the presence of cancer cells using for example,
Northern, dot blot or RT-PCR analysis to detect 151P3D4 expression.
The presence of RT-PCR amplifiable 151P3D4 mRNA provides an
indication of the presence of cancer. RT-PCR assays are well known
in the art. RT-PCR detection assays for tumor cells in peripheral
blood are currently being evaluated for use in the diagnosis and
management of a number of human solid tumors. In the prostate
cancer field, these include RT-PCR assays for the detection of
cells expressing PSA and PSM (Verkaik et al., 1997, Urol. Res.
25:373-384; Ghossein et al., 1995, J. Clin. Oncol. 13:1195-2000;
Heston et al., 1995, Clin. Chem 41:1687-1688).
[0260] A further aspect of the invention is an assessment of the
susceptibility that an individual has for developing cancer. In one
embodiment, a method for predicting susceptibility to cancer
comprises detecting 151P3D4 mRNA or 151P3D4 protein in a tissue
sample, its presence indicating susceptibility to cancer, wherein
the degree of 151P3D4 mRNA expression correlates to the degree of
susceptibility. In a specific embodiment, the presence of 151P3D4
in prostate or other tissue is examined, with the presence of
151P3D4 in the sample providing an indication of prostate cancer
susceptibility (or the emergence or existence of a prostate tumor).
Similarly, one can evaluate the integrity 151P3D4 nucleotide and
amino acid sequences in a biological sample, in order to identify
perturbations in the structure of these molecules such as
insertions, deletions, substitutions and the like. The presence of
one or more perturbations in 151P3D4 gene products in the sample is
an indication of cancer susceptibility (or the emergence or
existence of a tumor).
[0261] The invention also comprises methods for gauging tumor
aggressiveness. In one embodiment, a method for gauging
aggressiveness of a tumor comprises determining the level of
151P3D4 mRNA or 151P3D4 protein expressed by tumor cells, comparing
the level so determined to the level of 151P3D4 mRNA or 151P3D4
protein expressed in a corresponding normal tissue taken from the
same individual or a normal tissue reference sample, wherein the
degree of 151P3D4 mRNA or 151P3D4 protein expression in the tumor
sample relative to the normal sample indicates the degree of
aggressiveness. In a specific embodiment, aggressiveness of a tumor
is evaluated by determining the extent to which 151P3D4 is
expressed in the tumor cells, with higher expression levels
indicating more aggressive tumors. Another embodiment is the
evaluation of the integrity of 151P3D4 nucleotide and amino acid
sequences in a biological sample, in order to identify
perturbations in the structure of these molecules such as
insertions, deletions, substitutions and the like. The presence of
one or more perturbations indicates more aggressive tumors.
[0262] Another embodiment of the invention is directed to methods
for observing the progression of a malignancy in an individual over
time. In one embodiment, methods for observing the progression of a
malignancy in an individual over time comprise determining the
level of 151P3D4 mRNA or 151P3D4 protein expressed by cells in a
sample of the tumor, comparing the level so determined to the level
of 151P3D4 mRNA or 151P3D4 protein expressed in an equivalent
tissue sample taken from the same individual at a different time,
wherein the degree of 151P3D4 mRNA or 151P3D4 protein expression in
the tumor sample over time provides information on the progression
of the cancer. In a specific embodiment, the progression of a
cancer is evaluated by determining 151P3D4 expression in the tumor
cells over time, where increased expression over time indicates a
progression of the cancer. Also, one can evaluate the integrity
151P3D4 nucleotide and amino acid sequences in a biological sample
in order to identify perturbations in the structure of these
molecules such as insertions, deletions, substitutions and the
like, where the presence of one or more perturbations indicates a
progression of the cancer.
[0263] The above diagnostic approaches can be combined with any one
of a wide variety of prognostic and diagnostic protocols known in
the art. For example, another embodiment of the invention is
directed to methods for observing a coincidence between the
expression of 151P3D4 gene and 151P3D4 gene products (or
perturbations in 151P3D4 gene and 151P3D4 gene products) and a
factor that is associated with malignancy, as a means for
diagnosing and prognosticating the status of a tissue sample. A
wide variety of factors associated with malignancy can be utilized,
such as the expression of genes associated with malignancy (e.g.
PSA, PSCA and PSM expression for prostate cancer etc.) as well as
gross cytological observations (see, e.g., Bocking et al., 1984,
Anal. Quant. Cytol. 6(2):74-88; Epstein, 1995, Hum. Pathol.
26(2):223-9; Thorson et al., 199, Mod. Pathol. 11(6):543-51;
Baisden et al., 1999, Am. J. Surg. Pathol. 23(8):918-24). Methods
for observing a coincidence between the expression of 151P3D4 gene
and 151P3D4 gene products (or perturbations in 151P3D4 gene and
151P3D4 gene products) and another factor that is associated with
malignancy are useful, for example, because the presence of a set
of specific factors that coincide with disease provides information
crucial for diagnosing and prognosticating the status of a tissue
sample.
[0264] In one embodiment, methods for observing a coincidence
between the expression of 151P3D4 gene and 151P3D4 gene products
(or perturbations in 151P3D4 gene and 151P3D4 gene products) and
another factor associated with malignancy entails detecting the
overexpression of 151P3D4 mRNA or protein in a tissue sample,
detecting the overexpression of PSA mRNA or protein in a tissue
sample (or PSCA or PSM expression), and observing a coincidence of
151P3D4 mRNA or protein and PSA mRNA or protein overexpression (or
PSCA or PSM expression). In a specific embodiment, the expression
of 151P3D4 and PSA mRNA in prostate tissue is examined, where the
coincidence of 151P3D4 and PSA mRNA overexpression in the sample
indicates the existence of prostate cancer, prostate cancer
susceptibility or the emergence or status of a prostate tumor.
[0265] Methods for detecting and quantifying the expression of
151P3D4 mRNA or protein are described herein, and standard nucleic
acid and protein detection and quantification technologies are well
known in the art. Standard methods for the detection and
quantification of 151P3D4 mRNA include in situ hybridization using
labeled 151P3D4 riboprobes, Northern blot and related techniques
using 151P3D4 polynucleotide probes, RT-PCR analysis using primers
specific for 151P3D4, and other amplification type detection
methods, such as, for example, branched DNA, SISBA, TMA and the
like. In a specific embodiment, semi-quantitative RT-PCR is used to
detect and quantify 151P3D4 mRNA expression. Any number of primers
capable of amplifying 151P3D4 can be used for this purpose,
including but not limited to the various primer sets specifically
described herein. In a specific embodiment, polyclonal or
monoclonal antibodies specifically reactive with the wild-type
151P3D4 protein can be used in an immunohistochemical assay of
biopsied tissue.
[0266] IX.) Identification of Molecules that Interact with
151P3D4
[0267] The 151P3D4 protein and nucleic acid sequences disclosed
herein allow a skilled artisan to identify proteins, small
molecules and other agents that interact with 151P3D4, as well as
pathways activated by 151P3D4 via any one of a variety of art
accepted protocols. For example, one can utilize one of the
so-called interaction trap systems (also referred to as the
"two-hybrid assay"). In such systems, molecules interact and
reconstitute a transcription factor which directs expression of a
reporter gene, whereupon the expression of the reporter gene is
assayed. Other systems identify protein-protein interactions in
vivo through reconstitution of a eukaryotic transcriptional
activator, see, e.g., U.S. Pat. Nos. 5,955,280 issued Sep. 21,
1999, 5,925,523 issued Jul. 20, 1999, 5,846,722 issued Dec. 8, 1998
and 6,004,746 issued Dec. 21, 1999. Algorithms are also available
in the art for genome-based predictions of protein function (see,
e.g., Marcotte, et al., Nature 402: Nov. 4, 1999, 83-86).
[0268] Alternatively one can screen peptide libraries to identify
molecules that interact with 151P3D4 protein sequences. In such
methods, peptides that bind to 151P3D4 are identified by screening
libraries that encode a random or controlled collection of amino
acids. Peptides encoded by the libraries are expressed as fusion
proteins of bacteriophage coat proteins, the bacteriophage
particles are then screened against the 151P3D4 protein(s).
[0269] Accordingly, peptides having a wide variety of uses, such as
therapeutic, prognostic or diagnostic reagents, are thus identified
without any prior information on the structure of the expected
ligand or receptor molecule. Typical peptide libraries and
screening methods that can be used to identify molecules that
interact with 151P3D4 protein sequences are disclosed for example
in U.S. Pat. Nos. 5,723,286 issued Mar. 3, 1998 and 5,733,731
issued Mar. 31, 1998.
[0270] Alternatively, cell lines that express 151P3D4 are used to
identify protein-protein interactions mediated by 151P3D4. Such
interactions can be examined using immunoprecipitation techniques
(see, e.g., Hamilton B. J., et al. Biochem. Biophys. Res. Commun.
1999, 261:646-51). 151P3D4 protein can be immunoprecipitated from
151P3D4-expressing cell lines using anti-151P3D4 antibodies.
Alternatively, antibodies against His-tag can be used in a cell
line engineered to express fusions of 151P3D4 and a His-tag
(vectors mentioned above). The immunoprecipitated complex can be
examined for protein association by procedures such as Western
blotting, .sup.35S-methionine labeling of proteins, protein
microsequencing, silver staining and two-dimensional gel
electrophoresis.
[0271] Small molecules and ligands that interact with 151P3D4 can
be identified through related embodiments of such screening assays.
For example, small molecules can be identified that interfere with
protein function, including molecules that interfere with 151P3D4's
ability to mediate phosphorylation and de-phosphorylation,
interaction with DNA or RNA molecules as an indication of
regulation of cell cycles, second messenger signaling or
tumorigenesis. Similarly, small molecules that modulate
151P3D4-related ion channel, protein pump, or cell communication
functions are identified and used to treat patients that have a
cancer that expresses 151P3D4 (see, e.g., Hille, B., Ionic Channels
of Excitable Membranes 2.sup.nd Ed., Sinauer Assoc., Sunderland,
Mass., 1992). Moreover, ligands that regulate 151P3D4 function can
be identified based on their ability to bind 151P3D4 and activate a
reporter construct. Typical methods are discussed for example in
U.S. Pat. No. 5,928,868 issued Jul. 27, 1999, and include methods
for forming hybrid ligands in which at least one ligand is a small
molecule. In an illustrative embodiment, cells engineered to
express a fusion protein of 151P3D4 and a DNA-binding protein are
used to co-express a fusion protein of a hybrid ligand/small
molecule and a cDNA library transcriptional activator protein. The
cells further contain a reporter gene, the expression of which is
conditioned on the proximity of the first and second fusion
proteins to each other, an event that occurs only if the hybrid
ligand binds to target sites on both hybrid proteins. Those cells
that express the reporter gene are selected and the unknown small
molecule or the unknown ligand is identified. This method provides
a means of identifying modulators which activate or inhibit
151P3D4.
[0272] An embodiment of this invention comprises a method of
screening for a molecule that interacts with a 151P3D4 amino acid
sequence shown in FIG. 2 or FIG. 3, comprising the steps of
contacting a population of molecules with a 151P3D4 amino acid
sequence, allowing the population of molecules and the 151P3D4
amino acid sequence to interact under conditions that facilitate an
interaction, determining the presence of a molecule that interacts
with the 151P3D4 amino acid sequence, and then separating molecules
that do not interact with the 151P3D4 amino acid sequence from
molecules that do. In a specific. embodiment, the method further
comprises purifying, characterizing and identifying a molecule that
interacts with the 151P3D4 amino acid sequence. The identified
molecule can be used to modulate a function performed by 151P3D4.
In a preferred embodiment, the 151P3D4 amino acid sequence is
contacted with a library of peptides.
[0273] X.) Therapeutic Methods and Compositions
[0274] The identification of 151P3D4 as a protein that is normally
expressed in a restricted set of tissues, but which is also
expressed in prostate and other cancers, opens a number of
therapeutic approaches to the treatment of such cancers. As
contemplated herein, 151P3D4 functions as a transcription factor
involved in activating tumor-promoting genes or repressing genes
that block tumorigenesis.
[0275] Accordingly, therapeutic approaches that inhibit the
activity of a 151P3D4 protein are useful for patients suffering
from a cancer that expresses 151P3D4. These therapeutic approaches
generally fall into two classes. One class comprises various
methods for inhibiting the binding or association of a 151P3D4
protein with its binding partner or with other proteins. Another
class comprises a variety of methods for inhibiting the
transcription of a 151P3D4 gene or translation of 151P3D4 mRNA.
[0276] X.A.) Anti-Cancer Vaccines
[0277] The invention provides cancer vaccines comprising a
151P3D4-related protein or 151P3D4-related nucleic acid. In view of
the expression of 151P3D4, cancer vaccines prevent and/or treat
151P3D4-expressing cancers with minimal or no effects on non-target
tissues. The use of a tumor antigen in a vaccine that generates
humoral and/or cell-mediated immune responses as anti-cancer
therapy is well known in the art and has been employed in prostate
cancer using human PSMA and rodent PAP immunogens (Hodge et al.,
1995, Int. J. Cancer 63:231-237; Fong et al., 1997, J. Immunol.
159:3113-3117).
[0278] Such methods can be readily practiced by employing a
151P3D4-related protein, or a 151P3D4-encoding nucleic acid
molecule and recombinant vectors capable of expressing and
presenting the 151P3D4 immunogen (which typically comprises a
number of antibody or T cell epitopes). Skilled artisans understand
that a wide variety of vaccine systems for delivery of
immunoreactive epitopes are known in the art (see, e.g., Heryln et
al., Ann Med February 1999 31(1):66-78; Maruyama et al., Cancer
Immunol Immunother June 2000 49(3):123-32) Briefly, such methods of
generating an immune response (e.g. humoral and/or cell-mediated)
in a mammal, comprise the steps of: exposing the mammal's immune
system to an immunoreactive epitope (e.g. an epitope present in a
151P3D4 protein shown in FIG. 3 or analog or homolog thereof) so
that the mammal generates an immune response that is specific for
that epitope (e.g. generates antibodies that specifically recognize
that epitope). In a preferred method, a 151P3D4 immunogen contains
a biological motif, see e.g., Tables V-XVIII and XXII-LI, or a
peptide of a size range from 151P3D4 indicated in FIG. 5, FIG. 6,
FIG. 7, FIG. 8, and FIG. 9.
[0279] The entire 151P3D4 protein, immunogenic regions or epitopes
thereof can be combined and delivered by various means. Such
vaccine compositions can include, for example, lipopeptides (e.g.,
Vitiello, A. et al., J. Clin. Invest. 95:341, 1995), peptide
compositions encapsulated in poly(DL-lactide-co-glycolide) ("PLG")
microspheres (see, e.g., Eldridge, et al., Molec. Immunol.
28:287-294, 1991: Alonso et al., Vaccine 12:299-306, 1994; Jones et
al., Vaccine 13:675-681, 1995), peptide compositions contained in
immune stimulating complexes (ISCOMS) (see, e.g., Takahashi et al.,
Nature 344:873-875, 1990; Hu et al., Clin Exp Immunol. 113:235-243,
1998), multiple antigen peptide systems (MAPs) (see e.g., Tam, J.
P., Proc. Natl. Acad. Sci. U.S.A. 85:5409-5413, 1988; Tam, J. P.,
J. Immunol. Methods 196:17-32, 1996), peptides formulated as
multivalent peptides; peptides for use in ballistic delivery
systems, typically crystallized peptides, viral delivery vectors
(Perkus, M. E. et al., In: Concepts in vaccine development,
Kaufmann, S. H. E., ed., p. 379, 1996; Chakrabarti, S. et al.,
Nature 320:535, 1986; Hu, S. L. et al., Nature 320:537, 1986;
Kieny, M.-P. et al., AIDS Bio/Technology 4:790, 1986; Top, F. H. et
al., J. Infect. Dis. 124:148, 1971; Chanda, P. K. et al., Virology
175:535, 1990), particles of viral or synthetic origin (e.g.,
Kofler, N. et al., J. Immunol. Methods. 192:25, 1996; Eldridge, J.
H. et al., Sem. Hematol. 30:16, 1993; Falo, L. D., Jr. et al.,
Nature Med. 7:649, 1995), adjuvants (Warren, H. S., Vogel, F. R.,
and Chedid, L. A. Annu. Rev. Immunol. 4:369, 1986; Gupta, R. K. et
al., Vaccine 11:293, 1993), liposomes (Reddy, R. et al., J.
Immunol. 148:1585, 1992; Rock, K. L., Immunol. Today 17:131, 1996),
or, naked or particle absorbed cDNA (Ulmer, J. B. et al., Science
259:1745, 1993; Robinson, H. L., Hunt, L. A., and Webster, R. G.,
Vaccine 11:957, 1993; Shiver, J. W. et al., In: Concepts in vaccine
development, Kaufmann, S. H. E., ed., p. 423, 1996; Cease, K. B.,
and Berzofsky, J. A., Annu. Rev. Immunol. 12:923, 1994 and
Eldridge, J. H. et al., Sem. Hematol. 30:16, 1993). Toxin-targeted
delivery technologies, also known as receptor mediated targeting,
such as those of Avant Immunotherapeutics, Inc. (Needham, Mass.)
may also be used.
[0280] In patients with 151P3D4-associated cancer, the vaccine
compositions of the invention can also be used in conjunction with
other treatments used for cancer, e.g., surgery, chemotherapy, drug
therapies, radiation therapies, etc. including use in combination
with immune adjuvants such as IL-2, IL-12, GM-CSF, and the
like.
[0281] Cellular Vaccines:
[0282] CTL epitopes can be determined using specific algorithms to
identify peptides within 151P3D4 protein that bind corresponding
HLA alleles (see e.g., Table IV; Epimer.TM. and Epimatrix.TM.,
Brown University (URL
www.brown.edu/Research/TB-HIV_Lab/epimatrix/epimatrix.htm- l); and,
BIMAS, (URL bimas.dcrt.nih.gov/; SYFPEITHI at URL
syfpeithi.bmi-heidelberg.com/). In a preferred embodiment, a
151P3D4 immunogen contains one or more amino acid sequences
identified using techniques well known in the art, such as the
sequences shown in Tables V-XVIII and XXII-LI or a peptide of 8, 9,
10 or 11 amino acids specified by an HLA Class I motig/supermotif
(e.g., Table IV (A), Table IV (D), or Table IV (E)) and/or a
peptide of at least 9 amino acids that comprises an HLA Class II
motif/supermotif (e.g., Table IV (B) or Table IV (C)). As is
appreciated in the art, the HLA Class I binding groove is
essentially closed ended so that peptides of only a particular size
range can fit into the groove and be bound, generally HLA Class I
epitopes are 8, 9, 10, or 11 amino acids long. In contrast, the HLA
Class II binding groove is essentially open ended; therefore a
peptide of about 9 or more amino acids can be bound by an HLA Class
II molecule. Due to the binding groove differences between HLA
Class I and II, HLA Class I motifs are length specific, i.e.,
position two of a Class I motif is the second amino acid in an
amino to carboxyl direction of the peptide. The amino acid
positions in a Class II motif are relative only to each other, not
the overall peptide, i.e., additional amino acids can be attached
to the amino and/or carboxyl termini of a motif-bearing sequence.
HLA Class II epitopes are often 9, 10, 11, 12, 13, 14, 15, 16, 17,
18, 19, 20, 21, 22, 23, 24, or 25 amino acids long, or longer than
25 amino acids.
[0283] Antibody-Based Vaccines
[0284] A wide variety of methods for generating an immune response
in a mammal are known in the art (for example as the first step in
the generation of hybridomas). Methods of generating an immune
response in a mammal comprise exposing the mammal's immune system
to an immunogenic epitope on a protein (e.g. a 151P3D4 protein) so
that an immune response is generated. A typical embodiment consists
of a method for generating an immune response to 151P3D4 in a host,
by contacting the host with a sufficient amount of at least one
151P3D4 B cell or cytotoxic T-cell epitope or analog thereof; and
at least one periodic interval thereafter re-contacting the host
with the 151P3D4 B cell or cytotoxic T-cell epitope or analog
thereof. A specific embodiment consists of a method of generating
an immune response against a 151P3D4-related protein or a man-made
multiepitopic peptide comprising: administering 151P3D4 immunogen
(e.g. a 151P3D4 protein or a peptide fragment thereof, a 151P3D4
fusion protein or analog etc.) in a vaccine preparation to a human
or another mammal. Typically, such vaccine preparations further
contain a suitable adjuvant (see, e.g., U.S. Pat. No. 6,146,635) or
a universal helper epitope such as a PADRE.TM. peptide (Epimmune
Inc., San Diego, Calif; see, e.g., Alexander et al., J. Immunol.
2000 164(3); 164(3): 1625-1633; Alexander et al., Immunity 1994
1(9): 751-761 and Alexander et al., Immunol. Res. 1998 18(2):
79-92). An alternative method comprises generating an immune
response in an individual against a 151P3D4 immunogen by:
administering in vivo to muscle or skin of the individual's body a
DNA molecule that comprises a DNA sequence that encodes a 151P3D4
immunogen, the DNA sequence operatively linked to regulatory
sequences which control the expression of the DNA sequence; wherein
the DNA molecule is taken up by cells, the DNA sequence is
expressed in the cells and an immune response is generated against
the immunogen (see, e.g., U.S. Pat. No. 5,962,428). Optionally a
genetic vaccine facilitator such as anionic lipids; saponins;
lectins; estrogenic compounds; hydroxylated lower alkyls; dimethyl
sulfoxide; and urea is also administered. In addition, an
antiidiotypic antibody can be administered that mimics 151P3D4, in
order to generate a response to the target antigen.
[0285] Nucleic Acid Vaccines:
[0286] Vaccine compositions of the invention include nucleic
acid-mediated modalities. DNA or RNA that encode protein(s) of the
invention can be administered to a patient. Genetic immunization
methods can be employed to generate prophylactic or therapeutic
humoral and cellular immune responses directed against cancer cells
expressing 151P3D4. Constructs comprising DNA encoding a
151P3D4-related protein/immunogen and appropriate regulatory
sequences can be injected directly into muscle or skin of an
individual, such that the cells of the muscle or skin take-up the
construct and express the encoded 151P3D4 protein/immunogen.
Alternatively, a vaccine comprises a 151P3D4-related protein.
Expression of the 151P3D4-related protein immunogen results in the
generation of prophylactic or therapeutic humoral and cellular
immunity against cells that bear a 151P3D4 protein. Various
prophylactic and therapeutic genetic immunization techniques known
in the art can be used (for review, see information and references
published at Internet address www.genweb.com). Nucleic acid-based
delivery is described, for instance, in Wolff et. al., Science
247:1465 (1990) as well as U.S. Pat. Nos. 5,580,859; 5,589,466;
5,804,566; 5,739,118; 5,736,524; 5,679,647; WO 98/04720. Examples
of DNA-based delivery technologies include "naked DNA", facilitated
(bupivicaine, polymers, peptide-mediated) delivery, cationic lipid
complexes, and particle-mediated ("gene gun") or pressure-mediated
delivery (see, e.g., U.S. Pat. No. 5,922,687).
[0287] For therapeutic or prophylactic immunization purposes,
proteins of the invention can be expressed via viral or bacterial
vectors. Various viral gene delivery systems that can be used in
the practice of the invention include, but are not limited to,
vaccinia, fowlpox, canarypox, adenovirus, influenza, poliovirus,
adeno-associated virus, lentivirus, and sindbis virus (see, e.g.,
Restifo, 1996, Curr. Opin. Immunol. 8:658-663; Tsang et al. J.
Natl. Cancer Inst. 87:982-990 (1995)). Non-viral delivery systems
can also be employed by introducing naked DNA encoding a
151P3D4-related protein into the patient (e.g., intramuscularly or
intradermally) to induce an anti-tumor response.
[0288] Vaccinia virus is used, for example, as a vector to express
nucleotide sequences that encode the peptides of the invention.
Upon introduction into a host, the recombinant vaccinia virus
expresses the protein immunogenic peptide, and thereby elicits a
host immune response. Vaccinia vectors and methods useful in
immunization protocols are described in, e.g., U.S. Pat. No.
4,722,848. Another vector is BCG (Bacille Calmette Guerin). BCG
vectors are described in Stover et al., Nature 351:456-460(1991). A
wide variety of other vectors useful for therapeutic administration
or immunization of the peptides of the invention, e.g. adeno and
adeno-associated virus vectors, retroviral vectors, Salmonella
typhi vectors, detoxified anthrax toxin vectors, and the like, will
be apparent to those skilled in the art from the description
herein.
[0289] Thus, gene delivery systems are used to deliver a
151P3D4-related nucleic acid molecule. In one embodiment, the
full-length human 151P3D4 cDNA is employed. In another embodiment,
151P3D4 nucleic acid molecules encoding specific cytotoxic T
lymphocyte (CTL) and/or antibody epitopes are employed.
[0290] Ex Vivo Vaccines
[0291] Various ex vivo strategies can also be employed to generate
an immune response. One approach involves the use of antigen
presenting cells (APCs) such as dendritic cells (DC) to present
151P3D4 antigen to a patient's immune system. Dendritic cells
express MHC class I and II molecules, B7 co-stimulator, and IL-12,
and are thus highly specialized antigen presenting cells. In
prostate cancer, autologous dendritic cells pulsed with peptides of
the prostate-specific membrane antigen (PSMA) are being used in a
Phase I clinical trial to stimulate prostate cancer patients'
immune systems (Tjoa et al., 1996, Prostate 28:65-69; Murphy et
al., 1996, Prostate 29:371-380). Thus, dendritic cells can be used
to present 151P3D4 peptides to T cells in the context. of MHC class
I or II molecules. In one embodiment, autologous dendritic cells
are pulsed with 151P3D4 peptides capable of binding to MHC class I
and/or class II molecules. In another embodiment, dendritic cells
are pulsed with the complete 151P3D4 protein. Yet another
embodiment involves engineering the overexpression of a 151P3D4
gene in dendritic cells using various implementing vectors known in
the art, such as adenovirus (Arthur et al., 1997, Cancer Gene Ther.
4:17-25), retrovirus (Henderson et al., 1996, Cancer Res.
56:3763-3770), lentivirus, adeno-associated virus, DNA transfection
(Ribas et al., 1997, Cancer Res. 57:2865-2869), or tumor-derived
RNA transfection (Ashley et al., 1997, J. Exp. Med. 186:1177-1182).
Cells that express 151P3D4 can also be engineered to express immune
modulators, such as GM-CSF, and used as immunizing agents.
[0292] X.B.) 151P3D4 as a Target for Antibody-Based Therapy
[0293] 151P3D4 is an attractive target for antibody-based
therapeutic strategies. A number of antibody strategies are known
in the art for targeting both extracellular and intracellular
molecules (see, e.g., complement and ADCC mediated killing as well
as the use of intrabodies). Because 151P3D4 is expressed by cancer
cells of various lineages relative to corresponding normal cells,
systemic administration of 151P3D4-immunoreactive compositions are
prepared that exhibit excellent sensitivity without toxic,
non-specific and/or non-target effects caused by binding of the
immunoreactive composition to non-target organs and tissues.
Antibodies specifically reactive with domains of 151P3D4 are useful
to treat 151P3D4-expressing cancers systemically, either as
conjugates with a toxin or therapeutic agent, or as naked
antibodies capable of inhibiting cell proliferation or
function.
[0294] 151P3D4 antibodies can be introduced into a patient such
that the antibody binds to 151P3D4 and modulates a function, such
as an interaction with a binding partner, and consequently mediates
destruction of the tumor cells and/or inhibits the growth of the
tumor cells. Mechanisms by which such antibodies exert a
therapeutic effect can include complement-mediated cytolysis,
antibody-dependent cellular cytotoxicity, modulation of the
physiological function of 151P3D4, inhibition of ligand binding or
signal transduction pathways, modulation of tumor cell
differentiation, alteration of tumor angiogenesis factor profiles,
and/or apoptosis.
[0295] Those skilled in the art understand that antibodies can be
used to specifically target and bind immunogenic molecules such as
an immunogenic region of a 151P3D4 sequence shown in FIG. 2 or FIG.
3. In addition, skilled artisans understand that it is routine to
conjugate antibodies to cytotoxic agents (see, e.g., Slevers et al.
Blood 93:11 3678-3684 (Jun. 1, 1999)). When cytotoxic and/or
therapeutic agents are delivered directly to cells, such as by
conjugating them to antibodies specific for a molecule expressed by
that cell (e.g. 151P3D4), the cytotoxic agent will exert its known
biological effect (i.e. cytotoxicity) on those cells.
[0296] A wide variety of compositions and methods for using
antibody-cytotoxic agent conjugates to kill cells are known in the
art. In the context of cancers, typical methods entail
administering to an animal having a tumor a biologically effective
amount of a conjugate comprising a selected cytotoxic and/or
therapeutic agent linked to a targeting agent (e.g. an anti-151P3D4
antibody) that binds to a marker (e.g. 151P3D4) expressed,
accessible to binding or localized on the cell surfaces. A typical
embodiment is a method of delivering a cytotoxic and/or therapeutic
agent to a cell expressing 151P3D4, comprising conjugating the
cytotoxic agent to an antibody that immunospecifically binds to a
151P3D4 epitope, and, exposing the cell to the antibody-agent
conjugate. Another illustrative embodiment is a method of treating
an individual suspected of suffering from metastasized cancer,
comprising a step of administering parenterally to said individual
a pharmaceutical composition comprising a therapeutically effective
amount of an antibody conjugated to a cytotoxic and/or therapeutic
agent.
[0297] Cancer immunotherapy using anti-151P3D4 antibodies can be
done in accordance with various approaches that have been
successfully employed in the treatment of other types of cancer,
including but not limited to colon cancer (Arlen et al., 1998,
Crit. Rev. Immunol. 18:133-138), multiple myeloma (Ozaki et al.,
1997, Blood 90:3179-3186, Tsunenari et al., 1997, Blood
90:2437-2444), gastric cancer (Kasprzyk et al., 1992, Cancer Res.
52:2771-2776), B-cell lymphoma (Funakoshi et al., 1996, J.
Immunother. Emphasis Tumor Immunol. 19:93-101), leukemia (Zhong et
al., 1996, Leuk. Res. 20:581-589), colorectal cancer (Moun et al.,
1994, Cancer Res. 54:6160-6166; Velders et al., 1995, Cancer Res.
55:4398-4403), and breast cancer (Shepard et al., 1991, J. Clin.
Immunol. 11:117-127). Some therapeutic approaches involve
conjugation of naked antibody to a toxin or radioisotope, such as
the conjugation of Y.sup.91 or I.sup.131 to anti-CD20 antibodies
(e.g., Zevalin.TM., IDEC Pharmaceuticals Corp. or Bexxar.TM.,
Coulter Pharmaceuticals), while others involve co-administration of
antibodies and other therapeutic agents, such as Herceptin.TM.
(trastuzumab) with paclitaxel (Genentech, Inc.). The antibodies can
be conjugated to a therapeutic agent. To treat prostate cancer, for
example, 151P3D4 antibodies can be administered in conjunction with
radiation, chemotherapy or hormone ablation. Also, antibodies can
be conjugated to a toxin such as calicheamicin (e.g., Mylotarg.TM.,
Wyeth-Ayerst, Madison, N.J., a recombinant humanized IgG.sub.4
kappa antibody conjugated to antitumor antibiotic calicheamicin) or
a maytansinoid (e.g., taxane-based Tumor-Activated Prodrug, TAP,
platform, ImmunoGen, Cambridge, Mass., also see e.g., U.S. Pat. No.
5,416,064).
[0298] Although 151P3D4 antibody therapy is useful for all stages
of cancer, antibody therapy can be particularly appropriate in
advanced or metastatic cancers. Treatment with the antibody therapy
of the invention is indicated for patients who have received one or
more rounds of chemotherapy. Alternatively, antibody therapy of the
invention is combined with a chemotherapeutic or radiation regimen
for patients who have not received chemotherapeutic treatment.
Additionally, antibody therapy can enable the use of reduced
dosages of concomitant chemotherapy, particularly for patients who
do not tolerate the toxicity of the chemotherapeutic agent very
well. Fan et al. (Cancer Res. 53:4637-4642, 1993), Prewett et al.
(International J. of Onco. 9:217-224, 1996), and Hancock et al.
(Cancer Res. 51:4575-4580, 1991) describe the use of various
antibodies together with chemotherapeutic agents.
[0299] Although 151P3D4 antibody therapy is useful for all stages
of cancer, antibody therapy can be particularly appropriate in
advanced or metastatic cancers. Treatment with the antibody therapy
of the invention is indicated for patients who have received one or
more rounds of chemotherapy. Alternatively, antibody therapy of the
invention is combined with a chemotherapeutic or radiation regimen
for patients who have not received chemotherapeutic treatment.
Additionally, antibody therapy can enable the use of reduced
dosages of concomitant chemotherapy, particularly for patients who
do not tolerate the toxicity of the chemotherapeutic agent very
well.
[0300] Cancer patients can be evaluated for the presence and level
of 151P3D4 expression, preferably using immunohistochemical
assessments of tumor tissue, quantitative 151P3D4 imaging, or other
techniques that reliably indicate the presence and degree of
151P3D4 expression. Immunohistochemical analysis of tumor biopsies
or surgical specimens is preferred for this purpose. Methods for
immunohistochemical analysis of tumor tissues are well known in the
art.
[0301] Anti-151P3D4 monoclonal antibodies that treat prostate and
other cancers include those that initiate a potent immune response
against the tumor or those that are directly cytotoxic. In this
regard, anti-151P3D4 monoclonal antibodies (mAbs) can elicit tumor
cell lysis by either complement-mediated or antibody-dependent cell
cytotoxicity (ADCC) mechanisms, both of which require an intact Fc
portion of the immunoglobulin molecule for interaction with
effector cell Fc receptor sites on complement proteins. In
addition, anti-151P3D4 mAbs that exert a direct biological effect
on tumor growth are useful to treat cancers that express 151P3D4.
Mechanisms by which directly cytotoxic mAbs act include: inhibition
of cell growth, modulation of cellular differentiation, modulation
of tumor angiogenesis factor profiles, and the induction of
apoptosis. The mechanism(s) by which a particular anti-151P3D4 mAb
exerts an anti-tumor effect is evaluated using any number of in
vitro assays that evaluate cell death such as ADCC, ADMMC,
complement-mediated cell lysis, and so forth, as is generally known
in the art.
[0302] In some patients, the use of murine or other non-human
monoclonal antibodies, or human/mouse chimeric mAbs can induce
moderate to strong immune responses against the non-human antibody.
This can result in clearance of the antibody from circulation and
reduced efficacy. In the most severe cases, such an immune response
can lead to the extensive formation of immune complexes which,
potentially, can cause renal failure. Accordingly, preferred
monoclonal antibodies used in the therapeutic methods of the
invention are those that are either fully human or humanized and
that bind specifically to the target 151P3D4 antigen with high
affinity but exhibit low or no antigenicity in the patient.
[0303] Therapeutic methods of the invention contemplate the
administration of single anti-151P3D4 mAbs as well as combinations,
or cocktails, of different mAbs. Such mAb cocktails can have
certain advantages inasmuch as they contain mAbs that target
different epitopes, exploit different effector mechanisms or
combine directly cytotoxic mAbs with mAbs that rely on immune
effector functionality. Such mAbs in combination can exhibit
synergistic therapeutic effects. In addition, anti-151P3D4 mAbs can
be administered concomitantly with other therapeutic modalities,
including but not limited to various chemotherapeutic agents,
androgen-blockers, immune modulators (e.g., IL-2, GM-CSF), surgery
or radiation. The anti-151P3D4 mAbs are administered in their
"naked" or unconjugated form, or can have a therapeutic agent(s)
conjugated to them.
[0304] Anti-151P3D4 antibody formulations are administered via any
route capable of delivering the antibodies to a tumor cell. Routes
of administration include, but are not limited to, intravenous,
intraperitoneal, intramuscular, intratumor, intradermal, and the
like. Treatment generally involves repeated administration of the
anti-151P3D4 antibody preparation, via an acceptable route of
administration such as intravenous injection (IV), typically at a
dose in the range of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8,
0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25 mg/kg body
weight. In general, doses in the range of 10-1000 mg mAb per week
are effective and well tolerated.
[0305] Based on clinical experience with the Herceptin.TM. mAb in
the treatment of metastatic breast cancer, an initial loading dose
of approximately 4 mg/kg patient body weight IV, followed by weekly
doses of about 2 mg/kg IV of the anti-151P3D4 mAb preparation
represents an acceptable dosing regimen. Preferably, the initial
loading dose is administered as a 90 minute or longer infusion. The
periodic maintenance dose is administered as a 30 minute or longer
infusion, provided the initial dose was well tolerated. As
appreciated by those of skill in the art, various factors can
influence the ideal dose regimen in a particular case. Such factors
include, for example, the binding affinity and half life of the Ab
or mAbs used, the degree of 151P3D4 expression in the patient, the
extent of circulating shed 151P3D4 antigen, the desired
steady-state antibody concentration level, frequency of treatment,
and the influence of chemotherapeutic or other agents used in
combination with the treatment method of the invention, as well as
the health status of a particular patient.
[0306] Optionally, patients should be evaluated for the levels of
151P3D4 in a given sample (e.g. the levels of circulating 151P3D4
antigen and/or 151P3D4 expressing cells) in order to assist in the
determination of the most effective dosing regimen, etc. Such
evaluations are also used for monitoring purposes throughout
therapy, and are useful to gauge therapeutic success in combination
with the evaluation of other parameters (for example, urine
cytology and/or ImmunoCyt levels in bladder cancer therapy, or by
analogy, serum PSA levels in prostate cancer therapy).
[0307] Anti-idiotypic anti-151P3D4 antibodies can also be used in
anti-cancer therapy as a vaccine for inducing an immune response to
cells expressing a 151P3D4-related protein. In particular, the
generation of anti-idiotypic antibodies is well known in the art;
this methodology can readily be adapted to generate anti-idiotypic
anti-151P3D4 antibodies that mimic an epitope on a 151P3D4-related
protein (see, for example, Wagner et al., 1997, Hybridoma 16:
33-40; Foon et al., 1995, J. Clin. Invest. 96:334-342; Herlyn et
al., 1996, Cancer Immunol. Immunother. 43:65-76). Such an
anti-idiotypic antibody can be used in cancer vaccine
strategies.
[0308] X.C.) 151P3D4 as a Target for Cellular Immune Responses
[0309] Vaccines and methods of preparing vaccines that contain an
immunogenically effective amount of one or more HLA-binding
peptides as described herein are further embodiments of the
invention. Furthermore, vaccines in accordance with the invention
encompass compositions of one or more of the claimed peptides. A
peptide can be present in a vaccine individually. Alternatively,
the peptide can exist as a homopolymer comprising multiple copies
of the same peptide, or as a heteropolymer of various peptides.
Polymers have the advantage of increased immunological reaction
and, where different peptide epitopes are used to make up the
polymer, the additional ability to induce antibodies and/or CTLs
that react with different antigenic determinants of the pathogenic
organism or tumor-related peptide targeted for an immune response.
The composition can be a naturally occurring region of an antigen
or can be prepared, e.g., recombinantly or by chemical
synthesis.
[0310] Carriers that can be used with vaccines of the invention are
well known in the art, and include, e.g., thyroglobulin, albumins
such as human serum albumin, tetanus toxoid, polyamino acids such
as poly L-lysine, poly L-glutamic acid, influenza, hepatitis B
virus core protein, and the like. The vaccines can contain a
physiologically tolerable (i.e., acceptable) diluent such as water,
or saline, preferably phosphate buffered saline. The vaccines also
typically include an adjuvant. Adjuvants such as incomplete
Freund's adjuvant, aluminum phosphate, aluminum hydroxide, or alum
are examples of materials well known in the art. Additionally, as
disclosed herein, CTL responses can be primed by conjugating
peptides of the invention to lipids, such as
tripalmitoyl-S-glycerylcysteinlyseryl-serine (P.sub.3CSS).
Moreover, an adjuvant such as a synthetic
cytosine-phosphorothiolated-guanine-containi- ng (CpG)
oligonucleotides has been found to increase CTL responses 10- to
100-fold. (see, e.g. Davila and Celis, J. Immunol. 165:539-547
(2000))
[0311] Upon immunization with a peptide composition in accordance
with the invention, via injection, aerosol, oral, transdermal,
transmucosal, intrapleural, intrathecal, or other suitable routes,
the immune system of the host responds to the vaccine by producing
large amounts of CTLs and/or HTLs specific for the desired antigen.
Consequently, the host becomes at least partially immune to later
development of cells that express or overexpress 151P3D4 antigen,
or derives at least some therapeutic benefit when the antigen was
tumor-associated.
[0312] In some embodiments, it may be desirable to combine the
class I peptide components with components that induce or
facilitate neutralizing antibody and or helper T cell responses
directed to the target antigen. A preferred embodiment of such a
composition comprises class I and class II epitopes in accordance
with the invention. An alternative embodiment of such a composition
comprises a class I and/or class II epitope in accordance with the
invention, along with a cross reactive HTL epitope such as
PADRE.TM. (Epimmune, San Diego, Calif.) molecule (described eg., in
U.S. Pat. No. 5,736,142).
[0313] A vaccine of the invention can also include
antigen-presenting cells (APC), such as dendritic cells (DC), as a
vehicle to present peptides of the invention. Vaccine compositions
can be created in vitro, following dendritic cell mobilization and
harvesting, whereby loading of dendritic cells occurs in vitro. For
example, dendritic cells are transfected, e.g., with a minigene in
accordance with the invention, or are pulsed with peptides. The
dendritic cell can then be administered to a patient to elicit
immune responses in vivo. Vaccine compositions, either DNA- or
peptide-based, can also be administered in vivo in combination with
dendritic cell mobilization whereby loading of dendritic cells
occurs in vivo.
[0314] Preferably, the following principles are utilized when
selecting an array of epitopes for inclusion in a polyepitopic
composition for use in a vaccine, or for selecting discrete
epitopes to be included in a vaccine and/or to be encoded by
nucleic acids such as a minigene. It is preferred that each of the
following principles be balanced in order to make the selection.
The multiple epitopes to be incorporated in a given vaccine
composition may be, but need not be, contiguous in sequence in the
native antigen from which the epitopes are derived.
[0315] 1.) Epitopes are selected which, upon administration, mimic
immune responses that have been observed to be correlated with
tumor clearance. For HLA Class I this includes 3-4 epitopes that
come from at least one tumor associated antigen (TAA). For HLA
Class II a similar rationale is employed; again 3-4 epitopes are
selected from at least one TAA (see, e.g., Rosenberg et al.,
Science 278:1447-1450). Epitopes from one TAA may be used in
combination with epitopes from one or more additional TAAs to
produce a vaccine that targets tumors with varying expression
patterns of frequently-expressed TAAs.
[0316] 2.) Epitopes are selected that have the requisite binding
affinity established to be correlated with immunogenicity: for HLA
Class I an IC.sub.50 of 500 nM or less, often 200 nM or less; and
for Class II an IC.sub.50 of 1000 nM or less.
[0317] 3.) Sufficient supermotif bearing-peptides, or a sufficient
array of allele-specific motif-bearing peptides, are selected to
give broad population coverage. For example, it is preferable to
have at least 80% population coverage. A Monte Carlo analysis, a
statistical evaluation known in the art, can be employed to assess
the breadth, or redundancy of, population coverage.
[0318] 4.) When selecting epitopes from cancer-related antigens it
is often useful to select analogs because the patient may have
developed tolerance to the native epitope.
[0319] 5.) Of particular relevance are epitopes referred to as
"nested epitopes." Nested epitopes occur where at least two
epitopes overlap in a given peptide sequence. A nested peptide
sequence can comprise B cell, HLA class I and/or HLA class II
epitopes. When providing nested epitopes, a general objective is to
provide the greatest number of epitopes per sequence. Thus, an
aspect is to avoid providing a peptide that is any longer than the
amino terminus of the amino terminal epitope and the carboxyl
terminus of the carboxyl terminal epitope in the peptide. When
providing a multi-epitopic sequence, such as a sequence comprising
nested epitopes, it is generally important to screen the sequence
in order to insure that it does not have pathological or other
deleterious biological properties.
[0320] 6.) If a polyepitopic protein is created, or when creating a
minigene, an objective is to generate the smallest peptide that
encompasses the epitopes of interest. This principle is similar, if
not the same as that employed when selecting a peptide comprising
nested epitopes. However, with an artificial polyepitopic peptide,
the size minimization objective is balanced against the need to
integrate any spacer sequences between epitopes in the polyepitopic
protein. Spacer amino acid residues can, for example, be introduced
to avoid junctional epitopes (an epitope recognized by the immune
system, not present in the target antigen, and only created by the
man-made juxtaposition of epitopes), or to facilitate cleavage
between epitopes and thereby enhance epitope presentation.
Junctional epitopes are generally to be avoided because the
recipient may generate an immune response to that non-native
epitope. Of particular concern is a junctional epitope that is a
"dominant epitope." A dominant epitope may lead to such a zealous
response that immune responses to other epitopes are diminished or
suppressed.
[0321] 7.) Where the sequences of multiple variants of the same
target protein are present, potential peptide epitopes can also be
selected on the basis of their conservancy. For example, a
criterion for conservancy may define that the entire sequence of an
HLA class I binding peptide or the entire 9-mer core of a class II
binding peptide be conserved in a designated percentage of the
sequences evaluated for a specific protein antigen.
[0322] X.C.1. Minigene Vaccines
[0323] A number of different approaches are available which allow
simultaneous delivery of multiple epitopes. Nucleic acids encoding
the peptides of the invention are a particularly useful embodiment
of the invention. Epitopes for inclusion in a minigene are
preferably selected according to the guidelines set forth in the
previous section. A preferred means of administering nucleic acids
encoding the peptides of the invention uses minigene constructs
encoding a peptide comprising one or multiple epitopes of the
invention.
[0324] The use of multi-epitope minigenes is described below and
in, Ishioka et al., J. Immunol. 162:3915-3925, 1999; An, L. and
Whitton, J. L., J. Virol. 71:2292, 1997; Thomson, S. A. et al., J.
Immunol. 157:822, 1996; Whitton, J. L. et al., J. Virol. 67:348,
1993; Hanke, R. et al., Vaccine 16:426, 1998. For example, a
multi-epitope DNA plasmid encoding supermotif- and/or motif-bearing
epitopes derived 151P3D4, the PADRE.RTM. universal helper T cell
epitope or multiple HTL epitopes from 151P3D4 (see e.g., Tables
V-XVIII and XXII to LI), and an endoplasmic reticulum-translocating
signal sequence can be engineered. A vaccine may also comprise
epitopes that are derived from other TAAs.
[0325] The immunogenicity of a multi-epitopic minigene can be
confirmed in transgenic mice to evaluate the magnitude of CTL
induction responses against the epitopes tested. Further, the
immunogenicity of DNA-encoded epitopes in vivo can be correlated
with the in vitro responses of specific CTL lines against target
cells transfected with the DNA plasmid. Thus, these experiments can
show that the minigene serves to both: 1.) generate a CTL response
and 2.) that the induced CTLs recognized cells expressing the
encoded epitopes.
[0326] For example, to create a DNA sequence encoding the selected
epitopes (minigene) for expression in human cells, the amino acid
sequences of the epitopes may be reverse translated. A human codon
usage table can be used to guide the codon choice for each amino
acid. These epitope-encoding DNA sequences may be directly
adjoined, so that when translated, a continuous polypeptide
sequence is created. To optimize expression and/or immunogenicity,
additional elements can be incorporated into the minigene design.
Examples of amino acid sequences that can be reverse translated and
included in the minigene sequence include: HLA class I epitopes,
HLA class II epitopes, antibody epitopes, a ubiquitination signal
sequence, and/or an endoplasmic reticulum targeting signal. In
addition, HLA presentation of CTL and HTL epitopes may be improved
by including synthetic (e.g. poly-alanine) or naturally-occurring
flanking sequences adjacent to the CTL or HTL epitopes; these
larger peptides comprising the epitope(s) are within the scope of
the invention.
[0327] The minigene sequence may be converted to DNA by assembling
oligonucleotides that encode the plus and minus strands of the
minigene. Overlapping oligonucleotides (30-100 bases long) may be
synthesized, phosphorylated, purified and annealed under
appropriate conditions using well known techniques. The ends of the
oligonucleotides can be joined, for example, using T4 DNA ligase.
This synthetic minigene, encoding the epitope polypeptide, can then
be cloned into a desired expression vector.
[0328] Standard regulatory sequences well known to those of skill
in the art are preferably included in the vector to ensure
expression in the target cells. Several vector elements are
desirable: a promoter with a downstream cloning site for minigene
insertion; a polyadenylation signal for efficient transcription
termination; an E. coli origin of replication; and an E. coli
selectable marker (e.g. ampicillin or kanamycin resistance).
Numerous promoters can be used for this purpose, e.g., the human
cytomegalovirus (hCMV) promoter. See, e.g., U.S. Pat. Nos.
5,580,859 and 5,589,466 for other suitable promoter sequences.
[0329] Additional vector modifications may be desired to optimize
minigene expression and immunogenicity. In some cases, introns are
required for efficient gene expression, and one or more synthetic
or naturally-occurring introns could be incorporated into the
transcribed region of the minigene. The inclusion of mRNA
stabilization sequences and sequences for replication in mammalian
cells may also be considered for increasing minigene
expression.
[0330] Once an expression vector is selected, the minigene is
cloned into the polylinker region downstream of the promoter. This
plasmid is transformed into an appropriate E. coli strain, and DNA
is prepared using standard techniques. The orientation and DNA
sequence of the minigene, as well as all other elements included in
the vector, are confirmed using restriction mapping and DNA
sequence analysis. Bacterial cells harboring the correct plasmid
can be stored as a master cell bank and a working cell bank.
[0331] In addition, immunostimulatory sequences (ISSs or CpGs)
appear to play a role in the immunogenicity of DNA vaccines. These
sequences may be included in the vector, outside the minigene
coding sequence, if desired to enhance immunogenicity.
[0332] In some embodiments, a bi-cistronic expression vector which
allows production of both the minigene-encoded epitopes and a
second protein (included to enhance or decrease immunogenicity) can
be used. Examples of proteins or polypeptides that could
beneficially enhance the immune response if co-expressed include
cytokines (e.g., IL-2, IL-12, GM-CSF), cytokine-inducing molecules
(e.g., LeIF), costimulatory molecules, or for HTL responses, pan-DR
binding proteins (PADRE.TM., Epimmune, San Diego, Calif.). Helper
(HTL) epitopes can be joined to intracellular targeting signals and
expressed separately from expressed CTL epitopes; this allows
direction of the HTL epitopes to a cell compartment different than
that of the CTL epitopes. If required, this could facilitate more
efficient entry of HTL epitopes into the HLA class II pathway,
thereby improving HTL induction. In contrast to HTL or CTL
induction, specifically decreasing the immune response by
co-expression of immunosuppressive molecules (e.g. TGF.beta.,) may
be beneficial in certain diseases.
[0333] Therapeutic quantities of plasmid DNA can be produced for
example, by fermentation in E. coli, followed by purification.
Aliquots from the working cell bank are used to inoculate growth
medium, and grown to. saturation in shaker flasks or a bioreactor
according to well-known techniques. Plasmid DNA can be purified
using standard bioseparation technologies such as solid phase
anion-exchange resins supplied by QIAGEN, Inc. (Valencia, Calif.).
If required, supercoiled DNA can be isolated from the open circular
and linear forms using gel electrophoresis or other methods.
[0334] Purified plasmid DNA can be prepared for injection using a
variety of formulations. The simplest of these is reconstitution of
lyophilized DNA in sterile phosphate-buffer saline (PBS). This
approach, known as "naked DNA," is currently being used for
intramuscular (IM) administration in clinical trials. To maximize
the immunotherapeutic effects of minigene DNA vaccines, an
alternative method for formulating purified plasmid DNA may be
desirable. A variety of methods have been described, and new
techniques may become available. Cationic lipids, glycolipids, and
fusogenic liposomes can also be used in the formulation (see, e.g.,
as described by WO 93/24640; Mannino & Gould-Fogerite,
BioTechniques 6(7): 682 (1988); U.S. Pat No. 5,279,833; WO
91/06309; and Felgner, et al., Proc. Nat'l Acad. Sci. USA 84:7413
(1987). In addition, peptides and compounds referred to
collectively as protective, interactive, non-condensing compounds
(PINC) could also be complexed to purified plasmid DNA to influence
variables such as stability, intramuscular dispersion, or
trafficking to specific organs or cell types.
[0335] Target cell sensitization can be used as a functional assay
for expression and HLA class I presentation of minigene-encoded CTL
epitopes. For example, the plasmid DNA is introduced into a
mammalian cell line that is suitable as a target for standard CTL
chromium release assays. The transfection method used will be
dependent on the final formulation. Electroporation can be used for
"naked" DNA, whereas cationic lipids allow direct in vitro
transfection. A plasmid expressing green fluorescent protein (GFP)
can be co-transfected to allow enrichment of transfected cells
using fluorescence activated cell sorting (FACS). These cells are
then chromium-51 (.sup.51Cr) labeled and used as target cells for
epitope-specific CTL lines; cytolysis, detected by .sup.51Cr
release, indicates both production of, and HLA presentation of,
minigene-encoded CTL epitopes. Expression of HTL epitopes may be
evaluated in an analogous manner using assays to assess HTL
activity.
[0336] In vivo immunogenicity is a second approach for functional
testing of minigene DNA formulations. Transgenic mice expressing
appropriate human HLA proteins are immunized with the DNA product.
The dose and route of administration are formulation dependent
(e.g., IM for DNA in PBS, intraperitoneal (i.p.) for
lipid-complexed DNA). Twenty-one days after immunization,
splenocytes are harvested and restimulated for one week in the
presence of peptides encoding each epitope being tested.
Thereafter, for CTL effector cells, assays are conducted for
cytolysis of peptide-loaded, .sup.51Cr-labeled target cells using
standard techniques. Lysis of target cells that were sensitized by
HLA loaded with peptide epitopes, corresponding to minigene-encoded
epitopes, demonstrates DNA vaccine function for in vivo induction
of CTLs. Immunogenicity of HTL epitopes is confirmed in transgenic
mice in an analogous manner.
[0337] Alternatively, the nucleic acids can be administered using
ballistic delivery as described, for instance, in U.S. Pat. No.
5,204,253. Using this technique, particles comprised solely of DNA
are administered. In a further alternative embodiment, DNA can be
adhered to particles, such as gold particles.
[0338] Minigenes can also be delivered using other bacterial or
viral delivery systems well known in the art, e.g., an expression
construct encoding epitopes of the invention can be incorporated
into a viral vector such as vaccinia.
[0339] X.C.2. Combinations of CTL Peptides with Helper Peptides
[0340] Vaccine compositions comprising CTL peptides of the
invention can be modified, e.g., analoged, to provide desired
attributes, such as improved serum half life, broadened population
coverage or enhanced immunogenicity.
[0341] For instance, the ability of a peptide to induce CTL
activity can be enhanced by linking the peptide to a sequence which
contains at least one epitope that is capable of inducing a T
helper cell response. Although a CTL peptide can be directly linked
to a T helper peptide, often CTL epitope/HTL epitope conjugates are
linked by a spacer molecule. The spacer is typically comprised of
relatively small, neutral molecules, such as amino acids or amino
acid mimetics, which are substantially uncharged under
physiological conditions. The spacers are typically selected from,
e.g., Ala, Gly, or other neutral spacers of nonpolar amino acids or
neutral polar amino acids. It will be understood that the
optionally present spacer need not be comprised of the same
residues and thus may be a hetero- or homo-oligomer. When present,
the spacer will usually be at least one or two residues, more
usually three to six residues and sometimes 10 or more residues.
The CTL peptide epitope can be linked to the T helper peptide
epitope either directly or via a spacer either at the amino or
carboxy terminus of the CTL peptide. The amino terminus of either
the immunogenic peptide or the T helper peptide may be
acylated.
[0342] In certain embodiments, the T helper peptide is one that is
recognized by T helper cells present in a majority of a genetically
diverse population. This can be accomplished by selecting peptides
that bind to many, most, or all of the HLA class II molecules.
Examples of such amino acid bind many HLA Class II molecules
include sequences from antigens such as tetanus toxoid at positions
830-843 (QYIKANSKFIGITE; SEQ ID NO:______), Plasmodium falciparum
circumsporozoite (CS) protein at positions 378-398
(DIEKKIAKMEKASSVFNVVNS; SEQ ID NO:______), and Streptococcus 18kD
protein at positions 116-131 (GAVDSILGGVATYGAA; SEQ ID NO:______).
Other examples include peptides bearing a DR 1-4-7 supermotif, or
either of the DR3 motifs.
[0343] Alternatively, it is possible to prepare synthetic peptides
capable of stimulating T helper lymphocytes, in a loosely
HLA-restricted fashion, using amino acid sequences not found in
nature (see, e.g., PCT publication WO 95/07707). These synthetic
compounds called Pan-DR-binding epitopes (e.g., PADRE.TM.,
Epimmune, Inc., San Diego, Calif.) are designed to most preferably
bind most HLA-DR (human HLA class II) molecules. For instance, a
pan-DR-binding epitope peptide having the formula: aKXVAAWTLKAAa
(SEQ ID NO:______), where "X" is either cyclohexylalanine,
phenylalanine, or tyrosine, and a is either D-alanine or L-alanine,
has been found to bind to most HLA-DR alleles, and to stimulate the
response of T helper lymphocytes from most individuals, regardless
of their HLA type. An alternative of a pan-DR binding epitope
comprises all "L" natural amino acids and can be provided in the
form of nucleic acids that encode the epitope.
[0344] HTL peptide epitopes can also be modified to alter their
biological properties. For example, they can be modified to include
D-amino acids to increase their resistance to proteases and thus
extend their serum half life, or they can be conjugated to other
molecules such as lipids, proteins, carbohydrates, and the like to
increase their biological activity. For example, a T helper peptide
can be conjugated to one or more palmitic acid chains at either the
amino or carboxyl termini.
[0345] X.C.3. Combinations of CTL Peptides with T Cell Priming
Agents
[0346] In some embodiments it may be desirable to include in the
pharmaceutical compositions of the invention at least one component
which primes B lymphocytes or T lymphocytes. Lipids have been
identified as agents capable of priming CTL in vivo. For example,
palmitic acid residues can be attached to the .epsilon.- and
.alpha.-amino groups of a lysine residue and then linked, e.g., via
one or more linking residues such as Gly, Gly-Gly-, Ser, Ser-Ser,
or the like, to an immunogenic peptide. The lipidated peptide can
then be administered either directly in a micelle or particle,
incorporated into a liposome, or emulsified in an adjuvant, e.g.,
incomplete Freund's adjuvant. In a preferred embodiment, a
particularly effective immunogenic composition comprises palmitic
acid attached to .epsilon.- and .alpha.-amino groups of Lys, which
is attached via linkage, e.g., Ser-Ser, to the amino terminus of
the immunogenic peptide.
[0347] As another example of lipid priming of CTL responses, E.
coli lipoproteins, such as
tripalmitoyl-S-glycerylcysteinlyseryl-serine (P.sub.3CSS) can be
used to prime virus specific CTL when covalently attached to an
appropriate peptide (see, e.g., Deres, et al., Nature 342:561,
1989). Peptides of the invention can be coupled to P.sub.3CSS, for
example, and the lipopeptide administered to an individual to
specifically prime an immune response to the target antigen.
Moreover, because the induction of neutralizing antibodies can also
be primed with P.sub.3CSS-conjugated epitopes, two such
compositions can be combined to more effectively elicit both
humoral and cell-mediated responses.
[0348] X.C.4. Vaccine Compositions Comprising DC Pulsed with CTL
and/or HTL Peptides
[0349] An embodiment of a vaccine composition in accordance with
the invention comprises ex vivo administration of a cocktail of
epitope-bearing peptides to PBMC, or isolated DC therefrom, from
the patient's blood. A pharmaceutical to facilitate harvesting of
DC can be used, such as Progenipoietin.TM. (Pharmacia-Monsanto, St.
Louis, Mo.) or GM-CSF/IL-4. After pulsing the DC with peptides and
prior to reinfusion into patients, the DC are washed to remove
unbound peptides. In this embodiment, a vaccine comprises
peptide-pulsed DCs which present the pulsed peptide epitopes
complexed with HLA molecules on their surfaces.
[0350] The DC can be pulsed ex vivo with a cocktail of peptides,
some of which stimulate CTL responses to 151P3D4. Optionally, a
helper T cell (HTL) peptide, such as a natural or artificial
loosely restricted HLA Class II peptide, can be included to
facilitate the CTL response. Thus, a vaccine in accordance with the
invention is used to treat a cancer which expresses or
overexpresses 151P3D4.
[0351] X.D. Adoptive Immunotherapy
[0352] Antigenic 151P3D4-related peptides are used to elicit a CTL
and/or HTL response ex vivo, as well. The resulting CTL or HTL
cells, can be used to treat tumors in patients that do not respond
to other conventional forms of therapy, or will not respond to a
therapeutic vaccine peptide or nucleic acid in accordance with the
invention. Ex vivo CTL or HTL responses to a particular antigen are
induced by incubating in tissue culture the patient's, or
genetically compatible, CTL or HTL precursor cells together with a
source of antigen-presenting cells (APC), such as dendritic cells,
and the appropriate immunogenic peptide. After an appropriate
incubation time (typically about 7-28 days), in which the precursor
cells are activated and expanded into effector cells, the cells are
infused back into the patient, where they will destroy (CTL) or
facilitate destruction (HTL) of their specific target cell (e.g., a
tumor cell). Transfected dendritic cells may also be used as
antigen presenting cells.
[0353] X.E. Administration of Vaccines for Therapeutic or
Prophylactic Purposes
[0354] Pharmaceutical and vaccine compositions of the invention are
typically used to treat and/or prevent a cancer that expresses or
overexpresses 151P3D4. In therapeutic applications, peptide and/or
nucleic acid compositions are administered to a patient in an
amount sufficient to elicit an effective B cell, CTL and/or HTL
response to the antigen and to cure or at least partially arrest or
slow symptoms and/or complications. An amount adequate to
accomplish this is defined as "therapeutically effective dose."
Amounts effective for this use will depend on, e.g., the particular
composition administered, the manner of administration, the stage
and severity of the disease being treated, the weight and general
state of health of the patient, and the judgment of the prescribing
physician.
[0355] For pharmaceutical compositions, the immunogenic peptides of
the invention, or DNA encoding them, are generally administered to
an individual already bearing a tumor that expresses 151P3D4. The
peptides or DNA encoding them can be administered individually or
as fusions of one or more peptide sequences. Patients can be
treated with the immunogenic peptides separately or in conjunction
with other treatments, such as surgery, as appropriate.
[0356] For therapeutic use, administration should generally begin
at the first diagnosis of 151P3D4-associated cancer. This is
followed by boosting doses until at least symptoms are
substantially abated and for a period thereafter. The embodiment of
the vaccine composition (ie., including, but not limited to
embodiments such as peptide cocktails, polyepitopic polypeptides,
minigenes, or TAA-specific CTLs or pulsed dendritic cells)
delivered to the patient may vary according to the stage of the
disease or the patient's health status. For example, in a patient
with a tumor that expresses 151P3D4, a vaccine comprising
151P3D4-specific CTL may be more efficacious in killing tumor cells
in patient with advanced disease than alternative embodiments.
[0357] It is generally important to provide an amount of the
peptide epitope delivered by a mode of administration sufficient to
effectively stimulate a cytotoxic T cell response; compositions
which stimulate helper T cell responses can also be given in
accordance with this embodiment of the invention.
[0358] The dosage for an initial therapeutic immunization generally
occurs in a unit dosage range where the lower value is about 1, 5,
50, 500, or 1,000 .mu.g and the higher value is about 10,000;
20,000; 30,000; or 50,000 .mu.g. Dosage values for a human
typically range from about 500 .mu.g to about 50,000 .mu.g per 70
kilogram patient. Boosting dosages of between about 1.0 .mu.g to
about 50,000 .mu.g of peptide pursuant to a boosting regimen over
weeks to months may be administered depending upon the patient's
response and condition as determined by measuring the specific
activity of CTL and HTL obtained from the patient's blood.
Administration should continue until at least clinical symptoms or
laboratory tests indicate that the neoplasia, has been eliminated
or reduced and for a period thereafter. The dosages, routes of
administration, and dose schedules are adjusted in accordance with
methodologies known in the art.
[0359] In certain embodiments, the peptides and compositions of the
present invention are employed in serious disease states, that is,
life-threatening or potentially life threatening situations. In
such cases, as a result of the minimal amounts of extraneous
substances and the relative nontoxic nature of the peptides in
preferred compositions of the invention, it is possible and may be
felt desirable by the treating physician to administer substantial
excesses of these peptide compositions relative to these stated
dosage amounts.
[0360] The vaccine compositions of the invention can also be used
purely as prophylactic agents. Generally the dosage for an initial
prophylactic immunization generally occurs in a unit dosage range
where the lower value is about 1, 5, 50, 500, or 1000 .mu.g and the
higher value is about 10,000; 20,000; 30,000; or 50,000 .mu.g.
Dosage values for a human typically range from about 500 .mu.g to
about 50,000 .mu.g per 70 kilogram patient. This is followed by
boosting dosages of between about 1.0 .mu.g to about 50,000 .mu.g
of peptide administered at defined intervals from about four weeks
to six months after the initial administration of vaccine. The
immunogenicity of the vaccine can be assessed by measuring the
specific activity of CTL and HTL obtained from a sample of the
patient's blood.
[0361] The pharmaceutical compositions for therapeutic treatment
are intended for parenteral, topical, oral, nasal, intrathecal, or
local (e.g. as a cream or topical ointment) administration.
Preferably, the pharmaceutical compositions are administered
parentally, e.g., intravenously, subcutaneously, intradermally, or
intramuscularly. Thus, the invention provides compositions for
parenteral administration which comprise a solution of the
immunogenic peptides dissolved or suspended in an acceptable
carrier, preferably an aqueous carrier.
[0362] A variety of aqueous carriers may be used, e.g., water,
buffered water, 0.8% saline, 0.3% glycine, hyaluronic acid and the
like. These compositions may be sterilized by conventional,
well-known sterilization techniques, or may be sterile filtered.
The resulting aqueous solutions may be packaged for use as is, or
lyophilized, the lyophilized preparation being combined with a
sterile solution prior to administration.
[0363] The compositions may contain pharmaceutically acceptable
auxiliary substances as required to approximate physiological
conditions, such as pH-adjusting and buffering agents, tonicity
adjusting agents, wetting agents, preservatives, and the like, for
example, sodium acetate, sodium lactate, sodium chloride, potassium
chloride, calcium chloride, sorbitan monolaurate, triethanolarnine
oleate, etc.
[0364] The concentration of peptides of the invention in the
pharmaceutical formulations can vary widely, i.e., from less than
about 0.1%, usually at or at least about 2% to as much as 20% to
50% or more by weight, and will be selected primarily by fluid
volumes, viscosities, etc., in accordance with the particular mode
of administration selected.
[0365] A human unit dose form of a composition is typically
included in a pharmaceutical composition that comprises a human
unit dose of an acceptable carrier, in one embodiment an aqueous
carrier, and is administered in a volume/quantity that is known by
those of skill in the art to be used for administration of such
compositions to humans (see, e.g., Remington's Pharmaceutical
Sciences, 17.sup.th Edition, A. Gennaro, Editor, Mack Publishing
Co., Easton, Pa., 1985). For example a peptide dose for initial
immunization can be from about 1 to about 50,000 .mu.g, generally
100-5,000 .mu.g, for a 70 kg patient. For example, for nucleic
acids an initial immunization may be performed using an expression
vector in the form of naked nucleic acid administered IM (or SC or
ID) in the amounts of 0.5-5 mg at multiple sites. The nucleic acid
(0.1 to 1000 .mu.g) can also be administered using a gene gun.
Following an incubation period of 34 weeks, a booster dose is then
administered. The booster can be recombinant fowlpox virus
administered at a dose of 5-10.sup.7 to 5.times.10.sup.9 pfu.
[0366] For antibodies, a treatment generally involves repeated
administration of the anti-151P3D4 antibody preparation, via an
acceptable route of administration such as intravenous injection
(IV), typically at a dose in the range of about 0.1 to about 10
mg/kg body weight. In general, doses in the range of 10-500 mg mAb
per week are effective and well tolerated. Moreover, an initial
loading dose of approximately 4 mg/kg patient body weight IV,
followed by weekly doses of about 2 mg/kg IV of the anti-151P3D4
mAb preparation represents an acceptable dosing regimen. As
appreciated by those of skill in the art, various factors can
influence the ideal dose in a particular case. Such factors
include, for example, half life of a composition, the binding
affinity of an Ab, the immunogenicity of a substance, the degree of
151P3D4 expression in the patient, the extent of circulating shed
151P3D4 antigen, the desired steady-state concentration level,
frequency of treatment, and the influence of chemotherapeutic or
other agents used in combination with the treatment method of the
invention, as well as the health status of a particular patient.
Non-limiting preferred human unit doses are, for example, 500
.mu.g-1 mg, 1 mg-50 mg, 50 mg-100 mg, 100 mg-200 mg, 200 mg-300 mg,
400 mg-500 mg, 500 mg-600 mg, 600 mg-700 mg, 700 mg-800 mg, 800
mg-900 mg, 900 mg-1 g, or 1 mg-700 mg. In certain embodiments, the
dose is in a range of 2-5 mg/kg body weight, e.g., with follow on
weekly doses of 1-3 mg/kg; 0.5 mg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10
mg/kg body weight followed, e.g., in two, three or four weeks by
weekly doses; 0.5-10 mg/kg body weight, e.g., followed in two,
three or four weeks by weekly doses; 225, 250, 275, 300, 325, 350,
375, 400 mg m.sup.2 of body area weekly; 1-600 mg m.sup.2 of body
area weekly; 225-400 mg m.sup.2 of body area weekly; these does can
be followed by weekly doses for 2, 3, 4, 5, 6, 7, 8, 9, 19, 11, 12
or more weeks.
[0367] In one embodiment, human unit dose forms of polynucleotides
comprise a suitable dosage range or effective amount that provides
any therapeutic effect. As appreciated by one of ordinary skill in
the art a therapeutic effect depends on a number of factors,
including the sequence of the polynucleotide, molecular weight of
the polynucleotide and route of administration. Dosages are
generally selected by the physician or other health care
professional in accordance with a variety of parameters known in
the art, such as severity of symptoms, history of the patient and
the like. Generally, for a polynucleotide of about 20 bases, a
dosage range may be selected from, for example, an independently
selected lower limit such as about 0.1, 0.25, 0.5, 1, 2, 5, 10, 20,
30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400 or 500 mg/kg up to
an independently selected upper limit, greater than the lower
limit, of about 60, 80, 100, 200, 300, 400, 500, 750, 1000, 1500,
2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000 or 10,000 mg/kg. For
example, a dose may be about any of the following: 0.1 to 100
mg/kg, 0.1 to 50 mg/kg, 0.1 to 25 mg/kg, 0.1 to 10 mg/kg, 1 to 500
mg/kg, 100 to 400 mg/kg, 200 to 300 mg/kg, 1 to 100 mg/kg, 100 to
200 mg/kg, 300 to 400 mg/kg, 400 to 500 mg/kg, 500 to 1000 mg/kg,
500 to 5000 mg/kg, or 500 to 10,000 mg/kg. Generally, parenteral
routes of administration may require higher doses of polynucleotide
compared to more direct application to the nucleotide to diseased
tissue, as do polynucleotides of increasing length.
[0368] In one embodiment, human unit dose forms of T-cells comprise
a suitable dosage range or effective amount that provides any
therapeutic effect. As appreciated by one of ordinary skill in the
art, a therapeutic effect depends on a number of factors. Dosages
are generally selected by the physician or other health care
professional in accordance with a variety of parameters known in
the art, such as severity of symptoms, history of the patient and
the like. A dose may be about 10.sup.4 cells to about 10.sup.6
cells, about 10.sup.6 cells to about 10.sup.8 cells, about 10.sup.8
to about 10.sup.11 cells, or about 10.sup.8 to about
5.times.10.sup.10 cells. A dose may also about 10.sup.6
cells/m.sup.2 to about 10.sup.10 cells/m.sup.2, or about 10.sup.6
cells/m.sup.2 to about 10.sup.8 cells/m.sup.2.
[0369] Proteins(s) of the invention, and/or nucleic acids encoding
the protein(s), can also be administered via liposomes, which may
also serve to: 1) target the proteins(s) to a particular tissue,
such as lymphoid tissue; 2) to target selectively to diseases
cells; or, 3) to increase the half-life of the peptide composition.
Liposomes include emulsions, foams, micelles, insoluble monolayers,
liquid crystals, phospholipid dispersions, lamellar layers and the
like. In these preparations, the peptide to be delivered is
incorporated as part of a liposome, alone or in conjunction with a
molecule which binds to a receptor prevalent among lymphoid cells,
such as monoclonal antibodies which bind to the CD45 antigen, or
with other therapeutic or immunogenic compositions. Thus, liposomes
either filled or decorated with a desired peptide of the invention
can be directed to the site of lymphoid cells, where the liposomes
then deliver the peptide compositions. Liposomes for use in
accordance with the invention are formed from standard
vesicle-forming lipids, which generally include neutral and
negatively charged phospholipids and a sterol, such as cholesterol.
The selection of lipids is generally guided by consideration of,
e.g., liposome size, acid lability and stability of the liposomes
in the blood stream. A variety of methods are available for
preparing liposomes, as described in, e.g., Szoka, et al., Ann.
Rev. Biophys. Bioeng. 9:467 (1980), and U.S. Pat. Nos. 4,235,871,
4,501,728, 4,837,028, and 5,019,369.
[0370] For targeting cells of the immune system, a ligand to be
incorporated into the liposome can include, e.g., antibodies or
fragments thereof specific for cell surface determinants of the
desired immune system cells. A liposome suspension containing a
peptide may be administered intravenously, locally, topically, etc.
in a dose which varies according to, inter alia, the manner of
administration, the peptide being delivered, and the stage of the
disease being treated.
[0371] For solid compositions, conventional nontoxic solid carriers
may be used which include, for example, pharmaceutical grades of
mannitol, lactose, starch, magnesium stearate, sodium saccharin,
talcum, cellulose, glucose, sucrose, magnesium carbonate, and the
like. For oral administration, a pharmaceutically acceptable
nontoxic composition is formed by incorporating any of the normally
employed excipients, such as those carriers previously listed, and
generally 10-95% of active ingredient, that is, one or more
peptides of the invention, and more preferably at a concentration
of 25%-75%.
[0372] For aerosol administration, immunogenic peptides are
preferably supplied in finely divided form along with a surfactant
and propellant. Typical percentages of peptides are about 0.01%-20%
by weight, preferably about 1%-10%. The surfactant must, of course,
be nontoxic, and preferably soluble in the propellant.
Representative of such agents are the esters or partial esters of
fatty acids containing from about 6 to 22 carbon atoms, such as
caproic, octanoic, lauric, palmitic, stearic, linoleic, linolenic,
olesteric and oleic acids with an aliphatic polyhydric alcohol or
its cyclic anhydride. Mixed esters, such as mixed or natural
glycerides may be employed. The surfactant may constitute about
0.1%-20% by weight of the composition, preferably about 0.25-5%.
The balance of the composition is ordinarily propellant. A carrier
can also be included, as desired, as with, e.g., lecithin for
intranasal delivery.
[0373] XI.) Diagnostic and Prognostic Embodiments of 151P3D4.
[0374] As disclosed herein, 151P3D4 polynucleotides, polypeptides,
reactive cytotoxic T cells (CTL), reactive helper T cells (HTL) and
anti-polypeptide antibodies are used in well known diagnostic,
prognostic and therapeutic assays that examine conditions
associated with dysregulated cell growth such as cancer, in
particular the cancers listed in Table I (see, e.g., both its
specific pattern of tissue expression as well as its overexpression
in certain cancers as described for example in the Example entitled
"Expression analysis of 151P3D4 in normal tissues, and patient
specimens").
[0375] 151P3D4 can be analogized to a prostate associated antigen
PSA, the archetypal marker that has been used by medical
practitioners for years to identify and monitor the presence of
prostate cancer (see, e.g., Merrill et al., J. Urol. 163(2):
503-5120 (2000); Polascik et al., J. Urol. August; 162(2):293-306
(1999) and Fortier et al., J. Nat. Cancer Inst. 91(19):
1635-1640(1999)). A variety of other diagnostic markers are also
used in similar contexts including p53 and K-ras (see, e.g.,
Tulchinsky et al., Int J Mol Med Jul. 4, 1999 (1):99-102 and
Minimoto et al., Cancer Detect Prev 2000;24(1):1-12). Therefore,
this disclosure of 151P3D4 polynucleotides and polypeptides (as
well as 151P3D4 polynucleotide probes and anti-151P3D4 antibodies
used to identify the presence of these molecules) and their
properties allows skilled artisans to utilize these molecules in
methods that are analogous to those used, for example, in a variety
of diagnostic assays directed to examining conditions associated
with cancer.
[0376] Typical embodiments of diagnostic methods which utilize the
151P3D4 polynucleotides, polypeptides, reactive T cells and
antibodies are analogous to those methods from well-established
diagnostic assays which employ, e.g., PSA polynucleotides,
polypeptides, reactive T cells and antibodies. For example, just as
PSA polynucleotides are used as probes (for example in Northern
analysis, see, e.g., Sharief et al., Biochem. Mol. Biol. Int.
33(3):567-74(1994)) and primers (for example in PCR analysis, see,
e.g., Okegawa et al., J. Urol. 163(4): 1189-1190 (2000)) to observe
the presence and/or the level of PSA mRNAs in methods of monitoring
PSA overexpression or the metastasis of prostate cancers, the
151P3D4 polynucleotides described herein can be utilized in the
same way to detect 151P3D4 overexpression or the metastasis of
prostate and other cancers expressing this gene. Alternatively,
just as PSA polypeptides are used to generate antibodies specific
for PSA which can then be used to observe the presence and/or the
level of PSA proteins in methods to monitor PSA protein
overexpression (see, e.g., Stephan et al., Urology 55(4):560-3
(2000)) or the metastasis of prostate cells (see, e.g., Alanen et
al., Pathol. Res. Pract. 192(3):233-7 (1996)), the 151P3D4
polypeptides described herein can be utilized to generate
antibodies for use in detecting 151P3D4 overexpression or the
metastasis of prostate cells and cells of other cancers expressing
this gene.
[0377] Specifically, because metastases involves the movement of
cancer cells from an organ of origin (such as the lung or prostate
gland etc.) to a different area of the body (such as a lymph node),
assays which examine a biological sample for the presence of cells
expressing 151P3D4 polynucleotides and/or polypeptides can be used
to provide evidence of metastasis. For example, when a biological
sample from tissue that does not normally contain
151P3D4-expressing cells (lymph node) is found to contain
151P3D4-expressing cells such as the 151P3D4 expression seen in
LAPC4 and LAPC9, xenografts isolated from lymph node and bone
metastasis, respectively, this finding is indicative of
metastasis.
[0378] Alternatively 151P3D4 polynucleotides and/or polypeptides
can be used to provide evidence of cancer, for example, when cells
in a biological sample that do not normally express 151P3D4 or
express 151P3D4 at a different level are found to express 151P3D4
or have an increased expression of 151P3D4 (see, e.g., the 151P3D4
expression in the cancers listed in Table I and in patient samples
etc. shown in the accompanying Figures). In such assays, artisans
may further wish to generate supplementary evidence of metastasis
by testing the biological sample for the presence of a second
tissue restricted marker (in addition to 151P3D4) such as PSA, PSCA
etc. (see, e.g., Alanen et al., Pathol. Res. Pract. 192(3): 233-237
(1999)).
[0379] Just as PSA polynucleotide fragments and polynucleotide
variants are employed by skilled artisans for use in methods of
monitoring PSA, 151P3D4 polynucleotide fragments and polynucleotide
variants are used in an analogous manner. In particular, typical
PSA polynucleotides used in methods of monitoring PSA are probes or
primers which consist of fragments of the PSA cDNA sequence.
Illustrating this, primers used to PCR amplify a PSA polynucleotide
must include less than the whole PSA sequence to function in the
polymerase chain reaction. In the context of such PCR reactions,
skilled artisans generally create a variety of different
polynucleotide fragments that can be used as primers in order to
amplify different portions of a polynucleotide of interest or to
optimize amplification reactions (see, e.g., Caetano-Anolles, G.
Biotechniques 25(3): 472-476, 478-480 (1998); Robertson et al.,
Methods Mol. Biol. 98:121-154 (1998)). An additional illustration
of the use of such fragments is provided in the Example entitled
"Expression analysis of 151P3D4 in normal tissues, and patient
specimens," where a 151P3D4 polynucleotide fragment is used as a
probe to show the expression of 151P3D4 RNAs in cancer cells. In
addition, variant polynucleotide sequences are typically used as
primers and probes for the corresponding mRNAs in PCR and Northern
analyses (see, e.g., Sawai et al., Fetal Diagn. Ther. Nov.-Dec. 11,
1996(6):407-13 and Current Protocols In Molecular Biology, Volume
2, Unit 2, Frederick M. Ausubel et al., eds., 1995)).
Polynucleotide fragments and variants are useful in this context
where they are capable of binding to a target polynucleotide
sequence (e.g., a 151P3D4 polynucleotide shown in FIG. 2 or variant
thereof) under conditions of high stringency.
[0380] Furthermore, PSA polypeptides which contain an epitope that
can be recognized by an antibody or T cell that specifically binds
to that epitope are used in methods of monitoring PSA. 151P3D4
polypeptide fragments and polypeptide analogs or variants can also
be used in an analogous manner. This practice of using polypeptide
fragments or polypeptide variants to generate antibodies (such as
anti-PSA antibodies or T cells) is typical in the art with a wide
variety of systems such as fusion proteins being used by
practitioners (see, e.g., Current Protocols In Molecular Biology,
Volume 2, Unit 16, Frederick M. Ausubel et al. eds., 1995). In this
context, each epitope(s) functions to provide the architecture with
which an antibody or T cell is reactive. Typically, skilled
artisans create a variety of different polypeptide fragments that
can be used in order to generate immune responses specific for
different portions of a polypeptide of interest (see, e.g., U.S.
Pat. No. 5,840,501 and U S. Pat. No. 5,939,533). For example it may
be preferable to utilize a polypeptide comprising one of the
151P3D4 biological motifs discussed herein or a motif-bearing
subsequence which is readily identified by one of skill in the art
based on motifs available in the art. Polypeptide fragments,
variants or analogs are typically useful in this context as long as
they comprise an epitope capable of generating an antibody or T
cell specific for a target polypeptide sequence (e.g. a 151P3D4
polypeptide shown in FIG. 3).
[0381] As shown herein, the 151P3D4 polynucleotides and
polypeptides (as well as the 151P3D4 polynucleotide probes and
anti-151P3D4 antibodies or T cells used to identify the presence of
these molecules) exhibit specific properties that make them useful
in diagnosing cancers such as those listed in Table I. Diagnostic
assays that measure the presence of 151P3D4 gene products, in order
to evaluate the presence or onset of a disease condition described
herein, such as prostate cancer, are used to identify patients for
preventive measures or further monitoring, as has been done so
successfully with PSA. Moreover, these materials satisfy a need in
the art for molecules having similar or complementary
characteristics to PSA in situations where, for example, a definite
diagnosis of metastasis of prostatic origin cannot be made on the
basis of a test for PSA alone (see, e.g., Alanen et al., Pathol.
Res. Pract. 192(3): 233-237 (1996)), and consequently, materials
such as 151P3D4 polynucleotides and polypeptides (as well as the
151P3D4 polynucleotide probes and anti-151P3D4 antibodies used to
identify the presence of these molecules) need to be employed to
confirm a metastases of prostatic origin.
[0382] Finally, in addition to their use in diagnostic assays, the
151P3D4 polynucleotides disclosed herein have a number of other
utilities such as their use in the identification of oncogenetic
associated chromosomal abnormalities in the chromosomal region to
which the 151P3D4 gene maps (see the Example entitled "Chromosomal
Mapping of 151P3D4" below). Moreover, in addition to their use in
diagnostic assays, the 151P3D4-related proteins and polynucleotides
disclosed herein have other utilities such as their use in the
forensic analysis of tissues of unknown origin (see, e.g., Takahama
K Forensic Sci Int Jun. 28, 1996; 80(1-2): 63-9).
[0383] Additionally, 151P3D4-related proteins or polynucleotides of
the invention can be used to treat a pathologic condition
characterized by the over-expression of 151P3D4. For example, the
amino acid or nucleic acid sequence of FIG. 2 or FIG. 3, or
fragments of either, can be used to generate an immune response to
a 151P3D4 antigen. Antibodies or other molecules that react with
151P3D4 can be used to modulate the function of this molecule, and
thereby provide a therapeutic benefit.
[0384] XII.) Inhibition of 151P3D4 Protein Function
[0385] The invention includes various methods and compositions for
inhibiting the binding of 151P3D4 to its binding partner or its
association with other protein(s) as well as methods for inhibiting
151P3D4 function.
[0386] XII.A.) Inhibition of 151P3D4 with Intracellular
Antibodies
[0387] In one approach, a recombinant vector that encodes single
chain antibodies that specifically bind to 151P3D4 are introduced
into 151P3D4 expressing cells via gene transfer technologies.
Accordingly, the encoded single chain anti-151P3D4 antibody is
expressed intracellularly, binds to 151P3D4 protein, and thereby
inhibits its function. Methods for engineering such intracellular
single chain antibodies are well known. Such intracellular
antibodies, also known as "intrabodies", are specifically targeted
to a particular compartment within the cell, providing control over
where the inhibitory activity of the treatment is focused. This
technology has been successfully applied in the art (for review,
see Richardson and Marasco, 1995, TIBTECH vol. 13). Intrabodies
have been shown to virtually eliminate the expression of otherwise
abundant cell surface receptors (see, e.g., Richardson et al.,
1995, Proc. Natl. Acad. Sci. USA 92: 3137-3141; Beerli et al.,
1994, J. Biol. Chem. 289: 23931-23936; Deshane et al., 1994, Gene
Ther. 1: 332-337).
[0388] Single chain antibodies comprise the variable domains of the
heavy and light chain joined by a flexible linker polypeptide, and
are expressed as a single polypeptide. Optionally, single chain
antibodies are expressed as a single chain variable region fragment
joined to the light chain constant region. Well-known intracellular
trafficking signals are engineered into recombinant polynucleotide
vectors encoding such single chain antibodies in order to precisely
target the intrabody to the desired intracellular compartment. For
example, intrabodies targeted to the endoplasmic reticulum (ER) are
engineered to incorporate a leader peptide and, optionally, a
C-terminal ER retention signal, such as the KDEL amino acid motif
Intrabodies intended to exert activity in the nucleus are
engineered to include a nuclear localization signal. Lipid moieties
are joined to intrabodies in order to tether the intrabody to the
cytosolic side of the plasma membrane. Intrabodies can also be
targeted to exert function in the cytosol. For example, cytosolic
intrabodies are used to sequester factors within the cytosol,
thereby preventing them from being transported to their natural
cellular destination.
[0389] In one embodiment, intrabodies are used to capture 151P3D4
in the nucleus, thereby preventing its activity within the nucleus.
Nuclear targeting signals are engineered into such 151P3D4
intrabodies in order to achieve the desired targeting. Such 151P3D4
intrabodies are designed to bind specifically to a particular
151P3D4 domain. In another embodiment, cytosolic intrabodies that
specifically bind to a 151P3D4 protein are used to prevent 151P3D4
from gaining access to the nucleus, thereby preventing it from
exerting any biological activity within the nucleus (e.g.,
preventing 151P3D4 from forming transcription complexes with other
factors).
[0390] In order to specifically direct the expression of such
intrabodies to particular cells, the transcription of the intrabody
is placed under the regulatory control of an appropriate
tumor-specific promoter and/or enhancer. In order to target
intrabody expression specifically to prostate, for example, the PSA
promoter and/or promoter/enhancer can be utilized (See, for
example, U.S. Pat. No. 5,919,652 issued Jul. 6, 1999).
[0391] XII.B.) Inhibition of 151P3D4 with Recombinant Proteins
[0392] In another approach, recombinant molecules bind to 151P3D4
and thereby inhibit 151P3D4 function. For example, these
recombinant molecules prevent or inhibit 151P3D4 from
accessing/binding to its binding partner(s) or associating with
other protein(s). Such recombinant molecules can, for example,
contain the reactive part(s) of a 151P3D4 specific antibody
molecule. In a particular embodiment, the 151P3D4 binding domain of
a 151P3D4 binding partner is engineered into a dimeric fusion
protein, whereby the fusion protein comprises two 151P3D4 ligand
binding domains linked to the Fc portion of a human IgG, such as
human IgG1. Such IgG portion can contain, for example, the C.sub.H2
and C.sub.H3 domains and the hinge region, but not the C.sub.H1
domain. Such dirneric fusion proteins are administered in soluble
form to patients suffering from a cancer associated with the
expression of 151P3D4, whereby the dimeric fusion protein
specifically binds to 151P3D4 and blocks 151P3D4 interaction with a
binding partner. Such dimeric fusion proteins are further combined
into multimeric proteins using known antibody linking
technologies.
[0393] XII.C.) Inhibition of 151P3D4 Transcription or
Translation
[0394] The present invention also comprises various methods and
compositions for inhibiting the transcription of the 151P3D4 gene.
Similarly, the invention also provides methods and compositions for
inhibiting the translation of 151P3D4 mRNA into protein.
[0395] In one approach, a method of inhibiting the transcription of
the 151P3D4 gene comprises contacting the 151P3D4 gene with a
151P3D4 antisense polynucleotide. In another approach, a method of
inhibiting 151P3D4 mRNA translation comprises contacting a 151P3D4
mRNA with an antisense polynucleotide. In another approach, a
151P3D4 specific ribozyme is used to cleave a 151P3D4 message,
thereby inhibiting translation. Such antisense and ribozyme based
methods can also be directed to the regulatory regions of the
15P3D4 gene, such as 151P3D4 promoter and/or enhancer elements.
Similarly, proteins capable of inhibiting a 151P3D4 gene
transcription factor are used to inhibit 151P3D4 mRNA
transcription. The various polynucleotides and compositions useful
in the aforementioned methods have been described above. The use of
antisense and ribozyme molecules to inhibit transcription and
translation is well known in the art.
[0396] Other factors that inhibit the transcription of 151P3D4 by
interfering with 151P3D4 transcriptional activation are also useful
to treat cancers expressing 151P3D4. Similarly, factors that
interfere with 151P3D4 processing are useful to treat cancers that
express 151P3D4. Cancer treatment methods utilizing such factors
are also within the scope of the invention.
[0397] XII.D.) General Considerations for Therapeutic
Strategies
[0398] Gene transfer and gene therapy technologies can be used to
deliver therapeutic polynucleotide molecules to tumor cells
synthesizing 151P3D4 (i.e., antisense, ribozyme, polynucleotides
encoding intrabodies and other 151P3D4 inhibitory molecules). A
number of gene therapy approaches are known in the art. Recombinant
vectors encoding 151P3D4 antisense polynucleotides, ribozymes,
factors capable of interfering with 151P3D4 transcription, and so
forth, can be delivered to target tumor cells using such gene
therapy approaches.
[0399] The above therapeutic approaches can be combined with any
one of a wide variety of surgical, chemotherapy or radiation
therapy regimens. The therapeutic approaches of the invention can
enable the use of reduced dosages of chemotherapy (or other
therapies) and/or less frequent administration, an advantage for
all patients and particularly for those that do not tolerate the
toxicity of the chemotherapeutic agent well.
[0400] The anti-tumor activity of a particular composition (e.g.,
antisense, ribozyme, intrabody), or a combination of such
compositions, can be evaluated using various in vitro and in vivo
assay systems. In vitro assays that evaluate therapeutic activity
include cell growth assays, soft agar assays and other assays
indicative of tumor promoting activity, binding assays capable of
determining the extent to which a therapeutic composition will
inhibit the binding of 151P3D4 to a binding partner, etc.
[0401] In vivo, the effect of a 151P3D4 therapeutic composition can
be evaluated in a suitable animal model. For example, xenogenic
prostate cancer models can be used, wherein human prostate cancer
explants or passaged xenograft tissues are introduced into immune
compromised animals, such as nude or SCID mice (Klein et al., 1997,
Nature Medicine 3: 402-408). For example, PCT Patent Application
WO98/16628 and U.S. Pat. No. 6,107,540 describe various xenograft
models of human prostate cancer capable of recapitulating the
development of primary tumors, micrometastasis, and the formation
of osteoblastic metastases characteristic of late stage disease.
Efficacy can be predicted using assays that measure inhibition of
tumor formation, tumor regression or metastasis, and the like.
[0402] In vivo assays that evaluate the promotion of apoptosis are
useful in evaluating therapeutic compositions. In one embodiment,
xenografts from tumor bearing mice treated with the therapeutic
composition can be examined for the presence of apoptotic foci and
compared to untreated control xenograft-bearing mice. The extent to
which apoptotic foci are found in the tumors of the treated mice
provides an indication of the therapeutic efficacy of the
composition.
[0403] The therapeutic compositions used in the practice of the
foregoing methods can be formulated into pharmaceutical
compositions comprising a carrier suitable for the desired delivery
method. Suitable carriers include any material that when combined
with the therapeutic composition retains the anti-tumor function of
the therapeutic composition and is generally non-reactive with the
patient's immune system. Examples include, but are not limited to,
any of a number of standard pharmaceutical carriers such as sterile
phosphate buffered saline solutions, bacteriostatic water, and the
like (see, generally, Remington's Pharmaceutical Sciences 16.sup.th
Edition, A. Osal., Ed., 1980).
[0404] Therapeutic formulations can be solubilized and administered
via any route capable of delivering the therapeutic composition to
the tumor site. Potentially effective routes of administration
include, but are not limited to, intravenous, parenteral,
intraperitoneal, intramuscular, intratumor, intradermal,
intraorgan, orthotopic, and the like. A preferred formulation for
intravenous injection comprises the therapeutic composition in a
solution of preserved bacteriostatic water, sterile unpreserved
water, and/or diluted in polyvinylchloride or polyethylene bags
containing 0.9% sterile Sodium Chloride for Injection, USP.
Therapeutic protein preparations can be lyophilized and stored as
sterile powders, preferably under vacuum, and then reconstituted in
bacteriostatic water (containing for example, benzyl alcohol
preservative) or in sterile water prior to injection.
[0405] Dosages and administration protocols for the treatment of
cancers using the foregoing methods will vary with the method and
the target cancer, and will generally depend on a number of other
factors appreciated in the art.
[0406] XIII.) Kits
[0407] For use in the diagnostic and therapeutic applications
described herein, kits are also within the scope of the invention.
Such kits can comprise a carrier, package or container that is
compartmentalized to receive one or more containers such as vials,
tubes, and the like, each of the container(s) comprising one of the
separate elements to be used in the method. For example, the
container(s) can comprise a probe that is or can be detectably
labeled. Such probe can be an antibody or polynucleotide specific
for a 151P3D4-related protein or a 151P3D4 gene or message,
respectively. Where the method utilizes nucleic acid hybridization
to detect the target nucleic acid, the kit can also have containers
containing nucleotide(s) for amplification of the target nucleic
acid sequence and/or a container comprising a reporter-means, such
as a biotin-binding protein, such as avidin or streptavidin, bound
to a reporter molecule, such as an enzymatic, florescent, or
radioisotope label. The kit can include all or part of the amino
acid sequence of FIG. 2 or FIG. 3 or analogs thereof, or a nucleic
acid molecules that encodes such amino acid sequences.
[0408] The kit of the invention will typically comprise the
container described above and one or more other containers
comprising materials desirable from a commercial and user
standpoint, including buffers, diluents, filters, needles,
syringes, and package inserts with instructions for use.
[0409] A label can be present on the container to indicate that the
composition is used for a specific therapy or non-therapeutic
application, and can also indicate directions for either in vivo or
in vitro use, such as those described above. Directions and or
other information can also be included on an insert which is
included with the kit.
EXAMPLES
[0410] Various aspects of the invention are further described and
illustrated by way of the several examples that follow, none of
which are intended to limit the scope of the invention.
Example 1
[0411] SSH-Generated Isolation of a cDNA Fragment of the 151P3D4
Gene
[0412] To isolate genes that are over-expressed in bladder cancer
we used the Suppression Subtractive Hybridization (SSH) procedure
using cDNA derived from the LNCaP prostate cancer cell line.
[0413] The 151P3D4 SSH cDNA sequence was derived from a subtraction
consisting of two different populations of LNCaP cells. The 151P3D4
SSH cDNA sequence of417 bp is listed in FIG. 1.
[0414] The full-length 151P3D4 v.1 clone 1-placenta was cloned from
normal placenta cDNA, revealing an ORF of 354 amino acids (FIG. 2
and FIG. 3). Other variants of 151P3D4 were also identified and
these are listed in FIGS. 2 and 3.
[0415] Materials and Methods
[0416] Human Tissues:
[0417] The patient cancer and normal tissues were purchased from
different sources such as the NDRI (Philadelphia, Pa.). mRNA for
some normal tissues were purchased from Clontech, Palo Alto,
Calif.
[0418] RNA Isolation:
[0419] Tissues were homogenized in Trizol reagent (Life
Technologies, Gibco BRL) using 10 ml/g tissue isolate total RNA.
Poly A RNA was purified from total RNA using Qiagen's Oligotex mRNA
Mini and Midi kits. Total and mRNA were quantified by
spectrophotometric analysis (O.D. 260/280 nm) and analyzed by gel
electrophoresis.
[0420] Oligonucleotides:
[0421] The following HPLC purified oligonucleotides were used.
1 DPNCDN (cDNA synthesis primer): (SEQ ID NO:.sub.----)
5'TTTTGATCAAGCTT.sub.303' Adaptor 1: (SEQ ID NO:.sub.----)
5'CTAATACGACTCACTATAGGGCTCGAGCGGCCGCCCGGGC- AG3' (SEQ ID
NO:.sub.----) 3'GGCCCGTCCTAG5' Adaptor 2: (SEQ ID NO:.sub.----)
5'GTAATACGACTCACTATAGGGCAGCGTGGTCGCGGCCGAG3' (SEQ ID NO:.sub.----)
3'CGGCTCCTAG5' PCR primer 1: (SEQ ID NO:.sub.----)
5'CTAATACGACTCACTATAGGGC3' Nested primer (NP)1: (SEQ ID
NO:.sub.----) 5'TCGAGCGGCCGCCCGGGCAGGA3' Nested primer (NP)2: (SEQ
ID NO:.sub.----) 5'AGCGTGGTCGCGGCCGAGGA3'
[0422] Suppression Subtractive Hybridization:
[0423] Suppression Subtractive Hybridization (SSH) was used to
identify cDNAs corresponding to genes that may be differentially
expressed in prostate cancer. The SSH reaction utilized cDNA from
two different clones of LNCaP cells.
[0424] The gene 151P3D4 was derived from one population of LNCaP
cells minus another population of LNCaP cells cDNA subtraction. The
151P3D4 SSH DNA sequence (FIG. 1) was identified.
[0425] The cDNA derived from one population of LNCaP cells was used
as the source of the "driver" cDNA, while the cDNA from another
population of LNCaP cells was used as the source of the "tester"
cDNA. Double stranded cDNAs corresponding to tester and driver
cDNAs were synthesized from 2 .mu.g of poly(A).sup.+ RNA isolated
from the relevant tissue, as described above, using CLONTECH's
PCR-Select cDNA Subtraction Kit and 1 ng of oligonucleotide DPNCDN
as primer. First- and second-strand synthesis were carried out as
described in the Kit's user manual protocol (CLONTECH Protocol No.
PT1117-1, Catalog No. K1804-1). The resulting cDNA was digested
with Dpn II for 3 hrs at 37.degree. C. Digested cDNA was extracted
with phenolchloroform (1:1) and ethanol precipitated.
[0426] Driver cDNA was generated by combining in a 1:1 ratio Dpn II
digested cDNA from the relevant source (see above). Tester cDNA was
generated by diluting 1 .mu.l of Dpn II digested cDNA from the
relevant source (see above) (400 ng) in 5 .mu.l of water. The
diluted cDNA (2 .mu.l, 160 ng) was then ligated to 2 .mu.l of
Adaptor 1 and Adaptor 2 (10 .mu.M), in separate ligation reactions,
in a total volume of 10 .mu.l at 16.degree. C. overnight, using 400
u of T4 DNA ligase (CLONTECH). Ligation was terminated with 1 .mu.l
of 0.2 M EDTA and heating at 72.degree. C. for 5 min.
[0427] The first hybridization was performed by adding 1.5 .mu.l
(600 ng) of driver cDNA to each of two tubes containing 1.5 .mu.l
(20 ng) Adaptor 1- and Adaptor 2-ligated tester cDNA. In a final
volume of 4 .mu.l, the samples were overlaid with mineral oil,
denatured in an MJ Research thermal cycler at 98.degree. C. for 1.5
minutes, and then were allowed to hybridize for 8 hrs at 68.degree.
C. The two hybridizations were then mixed together with an
additional 1 .mu.l of fresh denatured driver cDNA and were allowed
to hybridize overnight at 68.degree. C. The second hybridization
was then diluted in 200 .mu.l of 20 mM Hepes, pH 8.3, 50 mM NaCl,
0.2 mM EDTA, heated at 70.degree. C. for 7 min. and stored at
-20.degree. C.
[0428] PCR Amplification Cloning and Sequencing of Gene Fragments
Generated from SSH:
[0429] To amplify gene fragments resulting from SSH reactions, two
PCR amplifications were performed. In the primary PCR reaction 1
.mu.l of the diluted final hybridization mix was added to 1 .mu.l
of PCR primer 1 (10 .mu.M), 0.5 .mu.l dNTP mix (10 .mu.M), 2.5
.mu.l 10.times. reaction buffer (CLONTECH) and 0.5 .mu.l 50.times.
Advantage cDNA polymerase Mix (CLONTECH) in a final volume of 25
.mu.l. PCR 1 was conducted using the following conditions:
75.degree. C. for 5 min., 94.degree. C. for 25 sec., then 27 cycles
of 94.degree. C. for 10 sec, 66.degree. C. for 30 sec, 72.degree.
C. for 1.5 min. Five separate primary PCR reactions were performed
for each experiment. The products were pooled and diluted 1:10 with
water. For the secondary PCR reaction, 1 .mu.l from the pooled and
diluted primary PCR reaction was added to the same reaction mix as
used for PCR 1, except that primers NP1 and NP2 (10 .mu.M) were
used instead of PCR primer 1. PCR 2 was performed using 10-12
cycles of 94.degree. C. for 10 sec, 68.degree. C. for 30 sec, and
72.degree. C. for 1.5 minutes. The PCR products were analyzed using
2% agarose gel electrophoresis.
[0430] The PCR products were inserted into pCR2.1 using the T/A
vector cloning kit (Invitrogen). Transformed E. coli were subjected
to blue/white and ampicillin selection. White colonies were picked
and arrayed into 96 well plates and were grown in liquid culture
overnight. To identify inserts, PCR amplification was performed on
1 ml of bacterial culture using the conditions of PCR1 and NP1 and
NP2 as primers. PCR products were analyzed using 2% agarose gel
electrophoresis.
[0431] Bacterial clones were stored in 20% glycerol in a 96 well
format. Plasmid DNA was prepared, sequenced, and subjected to
nucleic acid homology searches of the GenBank, dBest, and NCI-CGAP
databases.
[0432] RT-PCR Expression Analysis:
[0433] First strand cDNAs can be generated from 1 .mu.g of mRNA
with oligo (dT)12-18 priming using the Gibco-BRL Superscript
Preamplification system. The manufacturer's protocol was used which
included an incubation for 50 min at 42.degree. C. with reverse
transcriptase followed by RNAse H treatment at 37.degree. C. for 20
min. After completing the reaction, the volume can be increased to
200 .mu.l with water prior to normalization. First strand cDNAs
from 16 different normal human tissues can be obtained from
Clontech.
[0434] Normalization of the first strand cDNAs from multiple
tissues was performed by using the primers
5'atatcgccgcgctcgtcgtcgacaa3' (SEQ ID NO: ______) and
5'agccacacgcagctcattgtagaagg 3' (SEQ ID NO: _____) to amplify
.beta.-actin. First strand cDNA (5 .mu.l) were amplified in a total
volume of 50 .mu.l containing 0.4 .mu.M primers, 0.2 .mu.M each
dNTPs, 1XPCR buffer (Clontech, 10 mM Tris-HCL, 1.5 mM MgCl.sub.2,
50 mM KCl, pH8.3) and 1X Klentaq DNA polymerse (Clontech). Five
.mu.l of the PCR reaction can be removed at 18, 20, and 22 cycles
and used for agarose gel electrophoresis. PCR was performed using
an MJ Research thermal cycler under the following conditions:
initial denaturation can be at 94.degree. C. for 15 sec, followed
by a 18, 20, and 22 cycles of 94.degree. C. for 15, 65.degree. C.
for 2 min, 72.degree. C. for 5 sec. A final extension at 72.degree.
C. was carried out for 2 min. After agarose gel electrophoresis,
the band intensities of the 283 b.p. .beta.-actin bands from
multiple tissues were compared by visual inspection. Dilution
factors for the first strand cDNAs were calculated to result in
equal .beta.-actin band intensities in all tissues after 22 cycles
of PCR. Three rounds of normalization can be required to achieve
equal band intensities in all tissues after 22 cycles of PCR.
[0435] To determine expression levels of the 151P3D4 gene, 5 .mu.l
of normalized first strand cDNA were analyzed by PCR using 26, and
30 cycles of amplification. Semi-quantitative expression analysis
can be achieved by comparing the PCR products at cycle numbers that
give light band intensities. The primers used for RT-PCR were
designed using the 151P3D4 SSH sequence and are listed below:
2 151P3D4.1 5'-CCCACCAAACTGACCTATGATGAA-3' (SEQ ID NO: ) 151P3D4.2
5'-TGTATGCTCTGAAGCAGTAGACACC-3' (SEQ ID NO: )
[0436] A typical RT-PCR expression study is shown in FIG. 14. First
strand cDNA was prepared from vital pool 1 (liver, lung and
kidney), vital pool 2 (pancreas, colon and stomach), bladder cancer
pool, kidney cancer pool, colon cancer pool, lung cancer pool,
ovary cancer pool, breast cancer pool, and cancer metastasis pool.
Normalization was performed by PCR using primers to actin and
GAPDH. Semi-quantitative PCR, using primers to 151P3D4, was
performed at 26 and 30 cycles of amplification. Results show strong
expression of 151P3D4 in ovary cancer pool. Expression of 151P3D4
was also detected in bladder cancer pool, kidney cancer pool, colon
cancer pool, lung cancer pool, breast cancer pool, cancer
metastasis pool, vital pool 2, but not in vital pool 1.
[0437] Example 2
[0438] Full Length Cloning of 151P3D4
[0439] To isolate genes that are expressed in prostate cancer, we
used the Suppression Subtractive Hybridization (SSH) procedure
using cDNA derived from two different populations of LNCaP
cells.
[0440] The 151P3D4 SSH cDNA sequence was derived from a subtraction
consisting of one population of LNCaP cells minus another
population of LNCaP cells. The 151P3D4 SSH cDNA sequence of417 bp
is listed in FIG. 1.
[0441] The full-length 151P3D4 v.1 (151P3D4 clone 1-placenta) was
cloned from normal placenta cDNA, revealing an ORF of 354 amino
acids (FIG. 2 and FIG. 3). 151P3D4 v.1 showed 99% identity over
1492 nucleotides with the human mRNA for cartilage link protein
(gi463246) (FIG. 4A). 151P3D4 v.1 protein showed 100% identity over
354 amino acids with the human cartilage link protein (FIG. 4B).
Also, 151P3D4 v.1 was 96% identical over 355 amino acids with the
mouse link protein (gi4218976) (FIG. 4C)
[0442] Other variants of 151P3D4 were also identified and these are
listed in FIGS. 2 and 3. 151P3D4 v.2 codes for a novel protein that
contains sequences not present in 151P3D4 v.1. These are from amino
acids 1 to 400. Amino acids 401 to 721 of 151P3D4 v.2 align with
151P3D4 v.1 at positions 34 to 354 (FIG. 4D). A small portion of
151P3D4 v.2 demonstrates homology to the hypothetical protein
XP.sub.--094318 (FIG. 4E). The two proteins show 99% identity over
168 amino acids. The other variants 151P3D4 v.3 through v.11 each
differ from 151P3D4 v.1 by one nucleotide (FIG. 10).
[0443] Example 3
[0444] Chromosomal Mapping of 151P3D4
[0445] Chromosomal localization can implicate genes in disease
pathogenesis. Several chromosome mapping approaches are available
including fluorescent in situ hybridization (FISH), human/hamster
radiation hybrid (RH) panels (Walter et al., 1994; Nature Genetics
7:22; Research Genetics, Huntsville Ala.), human-rodent somatic
cell hybrid panels such as is available from the Coriell Institute
(Camden, N.J.), and genomic viewers utilizing BLAST homologies to
sequenced and mapped genomic clones (NCBI, Bethesda, Md.).
[0446] 151P3D4 maps to chromosome 5q13-q14.1 using 151P3D4 sequence
and the NCBI BLAST tool:
(http://www.ncbi.nlm.nih.gov/genome/seq/page.cgi?F=H-
sBlast.html&&ORG=Hs).
Example 4
[0447] Expression Analysis of 151P3D4 in Normal Tissues and Patient
Specimens
[0448] Expression analysis by RT-PCR demonstrated that 151P3D4 is
strongly expressed in cancer patient specimens (FIG. 14). First
strand cDNA was prepared from vital pool 1 (liver, lung and
kidney), vital pool 2 (pancreas, colon and stomach), bladder cancer
pool, kidney cancer pool, colon cancer pool, lung cancer pool,
ovary cancer pool, breast cancer pool, and cancer metastasis pool.
Normalization was performed by PCR using primers to actin and
GAPDH. Semi-quantitative PCR, using primers to 151P3D4, was
performed at 26 and 30 cycles of amplification. Results show strong
expression of 151P3D4 in ovary cancer pool. Expression of 151P3D4
was also detected in bladder cancer pool, kidney cancer pool, colon
cancer pool, lung cancer pool, breast cancer pool, cancer
metastasis pool, vital pool 2, but not in vital pool 1.
[0449] Extensive northern blot analysis of 151P3D4 in multiple
human normal tissues is shown in FIG. 15. Two multiple tissue
northern blots (Clontech) both with 2 .mu.g of mRNA/lane were
probed with the 151P3D4 SSH sequence. Size standards in kilobases
(kb) are indicated on the side. Results show expression of 151P3D4
in small intestine and placenta. Lower level expression was also
detected in heart and colon, but not in the other normal tissues
tested.
[0450] Expression of 151P3D4 in patient bladder cancer specimens is
shown in FIG. 16. RNA was extracted from normal bladder (NB),
bladder cancer cell lines (CL; UM-UC-3, J82, SCaBER), bladder
cancer patient tumors (T) and normal adjacent tissue (NAT).
Northern blots with 10 .mu.g of total RNA were probed with the
151P3D4 SSH sequence. Size standards in kilobases are indicated on
the side. Results show expression of 151P3D4 in patient bladder
cancer tissues, and in UM-UC-3 bladder cancer cell lines, but not
in normal bladder nor in the other bladder cancer cell lines
tested.
[0451] FIG. 17 shows that 151P3D4 was expressed in kidney cancer
patient specimens. RNA was extracted from kidney cancer cell lines
(CL: 769-P, A498, SW839), normal kidney (NK), kidney cancer patient
tumors (T) and their normal adjacent tissues (NAT). Northern blots
with 10 .mu.g of total RNA were probed with the 151P3D4 SSH
sequence. Size standards in kilobases are on the side. Results show
expression of 151P3D4 in patient kidney tumor tissues, but not in
normal kidney, nor in the cell lines tested.
[0452] Expression of 151P3D4 was also detected in ovary cancer
patient specimen (FIG. 18). RNA was extracted from ovary and
cervical cancer cell lines (CL), normal ovary (N), and ovary cancer
patient tumor (T). Northern blots with 10 .mu.g of total RNA were
probed with the 151P3D4 SSH sequence. Size standards in kilobases
are on the side. Results show strong expression of 151P3D4 in
patient ovary cancer tissues, but not in normal ovary nor in the
ovary and cervical cancer cell lines.
[0453] FIG. 19 shows that 151P3D4 was also expressed in stomach
cancers and in uterus cancers. Expression of 151P3D4 was assayed in
a panel of human stomach and uterus cancers (T) and their
respective matched normal tissues (N) on RNA dot blots. 151P3D4
expression was seen in both stomach and uterus cancers.
[0454] The restricted expression of 151P3D4 in normal tissues and
the expression detected in human cancers suggest that 151P3D4 is a
potential therapeutic target and a diagnostic marker for human
cancers.
Example 5
[0455] Transcript Variants of 151P3D4
[0456] Transcript variants are variants of matured mRNA from the
same gene by alternative transcription or alternative splicing.
Alternative transcripts are transcripts from the same gene but
start transcription at different points. Splice variants are mRNA
variants spliced differently from the same transcript. In
eukaryotes, when a multi-exon gene is transcribed from genomic DNA,
the initial RNA is spliced to produce functional mRNA, which has
only exons and is used for translation into an amino acid sequence.
Accordingly, a given gene can have zero to many alternative
transcripts and each transcript can have zero to many splice
variants. Each transcript variant has a unique exon makeup, and can
have different coding and/or non-coding (5' or 3' end) portions,
from the original transcript. Transcript variants can code for
similar or different proteins with the same or a similar function
or may encode proteins with different functions, and may be
expressed in the same tissue at the same time, or at different
tissue, or at different times, proteins encoded by transcript
variants can have similar or different cellular or extracellular
localizations, i.e., be secreted.
[0457] Transcript variants are identified by a variety of
art-accepted methods. For example, alternative transcripts and
splice variants are identified in a full-length cloning experiment,
or by use of full-length transcript and EST sequences. First, all
human ESTs were grouped into clusters which show direct or indirect
identity with each other. Second, ESTs in the same cluster were
further grouped into sub-clusters and assembled into a consensus
sequence. The original gene sequence is compared to the consensus
sequence(s) or other full-length sequences. Each consensus sequence
is a potential splice variant for that gene (see, e.g.,
http://www.doubletwist.com/products/c11_agentsOverview.jhtml). Even
when a variant is identified that is not a full-length clone, that
portion of the variant is very useful for antigen generation and
for further cloning of the full-length splice variant, using
techniques known in the art.
[0458] Moreover, computer programs are available in the art that
identify transcript variants based on genomic sequences.
Genomic-based transcript variant identification programs include
FgenesH (A. Salamov and V. Solovyev, "Ab initio gene finding in
Drosophila genomic DNA," Genome Research. April 2000;
10(4):516-22); Grail (http://compbio.ornl.gov/Grail-
-bin/EmptyGrailForm) and GenScan
(http://genes.mit.edu/GENSCAN.html). For a general discussion of
splice variant identification protocols see., e.g., Southan, C., A
genomic perspective on human proteases, FEBS Lett. Jun. 8, 2001;
498(2-3):214-8; de Souza, S. J., et al., Identification of human
chromosome 22 transcribed sequences with ORF expressed sequence
tags, Proc. Natl Acad Sci USA. Nov. 7, 2000; 97(23): 12690-3.
[0459] To further confirm the parameters of a transcript variant, a
variety of techniques are available in the art, such as full-length
cloning, proteomic validation, PCR-based validation, and 5' RACE
validation, etc. (see e.g., Proteomic Validation: Brennan, S. O.,
et al., Albumin banks peninsula: a new termination variant
characterized by electrospray mass spectrometry, Biochem Biophys
Acta. Aug. 17, 1999; 1433(1-2):321-6; Ferranti P, et al.,
Differential splicing of pre-messenger RNA produces multiple forms
of mature caprine alpha(s1)-casein, Eur J Biochem. Oct. 1, 1997;
249(1): 1-7. For PCR-based Validation: Wellmann S, et al., Specific
reverse transcription-PCR quantification of vascular endothelial
growth factor (VEGF) splice variants by LightCycler technology,
Clin Chem. April 2001; 47(4):654-60; Jia, H. P., et al., Discovery
of new human beta-defensins using a genomics-based approach, Gene.
Jan. 24, 2001; 263(1-2):211-8. For PCR-based and 5' RACE
Validation: Brigle, K. E., et al., Organization of the murine
reduced folate carrier gene and identification of variant splice
forms, Biochem Biophys Acta. Aug. 7, 1997; 1353(2): 191-8).
[0460] It is known in the art that genomic regions are modulated in
cancers. When the genomic region to which a gene maps is modulated
in a particular cancer, the alternative transcripts or splice
variants of the gene are modulated as well. Disclosed herein is
that 151P3D4 has a particular expression profile. Alternative
transcripts and splice variants of 151P3D4 that are structurally
and/or functionally similar to 151P3D4 share this expression
pattern, thus serving as tumor associated markers/antigens.
[0461] The exon composition of the original transcript, designated
as 151P3D4 v.1, is shown in Table LII (A). Using the full-length
gene and EST sequences, one alternative transcript was identified,
designated as 151P3D4 v.2. Compared with 151P3D4 v.1, transcript
variant 151P3D4 v.2 has 10 exons, as shown in Table LII (B) and
FIG. 12. Exons 8 and 9 are the same as exons 3 and 4 of 151P3D4
v.1, and exon 10 is the coding portion of exon 5 of 151P3D4 v.1.
Each different combination of exons in spatial order, e.g. exons 2
and 3, is a potential splice variant. FIG. 12 shows the schematic
alignment of exons of the two transcript variants.
[0462] Table LIII shows nucleotide sequence of the transcript
variant, 151P3D4 v.2 (see also FIG. 2B). Table LIV shows the
alignment of the transcript variant 151P3D4 v.2 with nucleic acid
sequence of 151P3D4 v.1. FIG. 3B provides the amino acid
translation of the transcript variant 151P3D4 v.2 for the
identified reading frame orientation. Table LV displays alignments
of the amino acid sequence encoded by the transcript variant
151P3D4 v.2 with that of 151P3D4 v.1.
Example 6
[0463] Single Nucleotide Polymorphisms of 151P3D4
[0464] Single Nucleotide Polymorphism (SNP) is a single base pair
variation in nucleotide sequences. At a specific point of the
genome, there are four possible nucleotide base pairs: A/T, C/G,
G/C and T/A. Genotype refers to the base pair make-up of one or
more spots in the genome of an individual, while haplotype refers
to base pair make-up of more than one varied spots on the same DNA
molecule (chromosome in higher organism). SNPs that occur on a cDNA
are called cSNPs. These cSNPs may change amino acids of the protein
encoded by the gene and thus change the functions of the protein.
Some SNPs cause inherited diseases and some others contribute to
quantitative variations in phenotype and reactions to environmental
factors including diet and drugs among individuals. Therefore, SNPs
and/or combinations of alleles (called haplotypes) have many
applications including diagnosis of inherited diseases,
determination of drug reactions and dosage, identification of genes
responsible for disearses and discovery of genetic relationship
between individuals (P. Nowotny, J. M. Kwon and A. M. Goate, "SNP
analysis to dissect human traits," Curr. Opin. Neurobiol. October
2001; 11(5):637-641; M. Pirmohamed and B. K. Park, "Genetic
susceptibility to adverse drug reactions," Trends Pharmacol. Sci.
June 2001; 22(6):298-305; J. H. Riley, C. J. Allan, E. Lai and A.
Roses, "The use of single nucleotide polymorphisms in the isolation
of common disease genes," Pharmacogenomics. February 2000;
1(1):39-47; R. Judson, J. C. Stephens and A. Windemuth, "The
predictive power of haplotypes in clinical response,"
Pharmacogenomics. February 2000; 1(1):15-26).
[0465] SNPs are identified by a variety of art-accepted methods (P.
Bean, "The promising voyage of SNP target discovery," Am. Clin.
Lab. October-November; 2001; 20(9): 18-20; K. M. Weiss, "In search
of human variation," Genome Res. July 1998; 8(7):691-697; M. M.
She, "Enabling large-scale pharmacogenetic studies by
high-throughput mutation detection and genotyping technologies,"
Clin. Chem. February 2001; 47(2): 164-172). For example, SNPs are
identified by sequencing DNA fragments that show polymorphism by
gel-based methods such as restriction fragment length polymorphism
(RFLP) and denaturing gradient gel electrophoresis (DGGE). They can
also be discovered by direct sequencing of DNA samples pooled from
different individuals or by comparing sequences from different DNA
samples. With the rapid accumulation of sequence data in public and
private databases, one can discover SNPs by comparing sequences
using computer programs (Z. Gu, L. Hillier and P. Y. Kwok, "Single
nucleotide polymorphism hunting in cyberspace," Hum. Mutat. 1998;
12(4):221-225). SNPs can be verified and genotype or haplotype of
an individual can be determined by a variety of methods including
direct sequencing and high throughput microarrays (P. Y. Kwok,
"Methods for genotyping single nucleotide polymorphisms," Annu.
Rev. Genomics Hum. Genet. 2001; 2:235-258; M. Kokoris, K. Dix, K.
Moynihan, J. Mathis, B. Erwin, P. Grass, B. Hines and A.
Duesterhoeft, "High-throughput SNP genotyping with the Masscode
system," Mol. Diagn. December 2000; 5(4):329-340).
[0466] Using the methods described above, nine SNPs were identified
in the original transcript, 151P3D4 v.1, at positions 154 (A/G),
218 (C/G), 219 (G/C), 999 (C/G), 1326 (C/T), 1399 (T/C), 1400
(C/T), 1653 (T/C) and 1726 (A/G). The transcripts or proteins with
alternative alleles were designated as variants 151P3D4 v.3, v.4,
v.5, v.6, v.7, v.8, v.9, v.10 and v.11. FIGS. 10 and 12 show the
schematic alignment of the nucleotide variants. FIG. 11 shows the
schematic alignment of protein variants, corresponding to
nucleotide variants. Nucleotide variants that code for the same
amino acid sequence as variant 1 are not shown in FIG. 11. These
alleles of the SNPs, though shown separately here, can occur in
different combinations (haplotypes) and in any one of the
transcript variants that contains the sequence context of the SNPs,
e.g., 151P3D4 v.7.
Example 7
[0467] Production of Recombinant 151P3D4 in Prokaryotic Systems
[0468] To express recombinant 151P3D4 and 151P3D4 variants in
prokaryotic cells, the full or partial length 151P3D4 and 151P3D4
variant cDNA sequences are cloned into any one of a variety of
expression vectors known in the art. One or more of the following
regions of 151P3D4 variants are expressed: the full length sequence
presented in FIGS. 2 and 3, or any 8, 9, 10, 11, 12, 13, 14, 15,
16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more
contiguous amino acids from 151P3D4, variants, or analogs
thereof.
[0469] A. In vitro Transcription and Translation Constructs:
[0470] pCRII: To generate 151P3D4 sense and anti-sense RNA probes
for RNA in situ investigations, pCRII constructs (Invitrogen,
Carlsbad Calif.) are generated encoding either all or fragments of
the 151P3D4 cDNA. The pCRII vector has Sp6 and T7 promoters
flanking the insert to drive the transcription of 151P3D4 RNA for
use as probes in RNA in situ hybridization experiments. These
probes are used to analyze the cell and tissue expression of
151P3D4 at the RNA level. Transcribed 151P3D4 RNA representing the
cDNA amino acid coding region of the 151P3D4 gene is used in in
vitro translation systems such as the TnT.TM. Coupled
Reticulolysate System (Promega, Corp., Madison, Wis.) to synthesize
151P3D4 protein.
[0471] B. Bacterial Constructs:
[0472] PGEX Constructs: To generate recombinant 151P3D4 proteins in
bacteria that are fused to the Glutathione S-transferase (GST)
protein, all or parts of the 151P3D4 cDNA protein coding sequence
are cloned into the pGEX family of GST-fusion vectors (Amersham
Pharmacia Biotech, Piscataway, N.J.). These constructs allow
controlled expression of recombinant 151P3D4 protein sequences with
GST fused at the amino-terminus and a six histidine epitope (6X
His) at the carboxyl-terminus. The GST and 6X His tags permit
purification of the recombinant fusion protein from induced
bacteria with the appropriate affinity matrix and allow recognition
of the fusion protein with anti-GST and anti-His antibodies. The 6X
His tag is generated by adding 6 histidine codons to the cloning
primer at the 3' end, e.g., of the open reading frame (ORF). A
proteolytic cleavage site, such as the PreScission.TM. recognition
site in pGEX-6P-1, may be employed such that it permits cleavage of
the GST tag from 151P3D4-related protein. The ampicillin resistance
gene and pBR322 origin permits selection and maintenance of the
pGEX plasmids in E. coli.
[0473] pMAL Constructs: To generate, in bacteria, recombinant
151P3D4 proteins that are fused to maltose-binding protein (MBP),
all or parts of the 151P3D4 cDNA protein coding sequence are fused
to the MBP gene by cloning into the pMAL-c2X and pMAL-p2X vectors
(New England Biolabs, Beverly, Mass.). These constructs allow
controlled expression of recombinant 151P3D4 protein sequences with
MBP fused at the amino-terminus and a 6X His epitope tag at the
carboxyl-terminus. The MBP and 6X His tags permit purification of
the recombinant protein from induced bacteria with the appropriate
affinity matrix and allow recognition of the fusion protein with
anti-MBP and anti-His antibodies. The 6X His epitope tag is
generated by adding 6 histidine codons to the 3' cloning primer. A
Factor Xa recognition site permits cleavage of the pMAL tag from
151P3D4. The pMAL-c2X and pMAL-p2X vectors are optimized to express
the recombinant protein in the cytoplasm or periplasm respectively.
Periplasm expression enhances folding of proteins with disulfide
bonds.
[0474] pET Constructs: To express 151P3D4 in bacterial cells, all
or parts of the 151P3D4 cDNA protein coding sequence are cloned
into the pET family of vectors (Novagen, Madison, Wis.). These
vectors allow tightly controlled expression of recombinant 151P3D4
protein in bacteria with and without fusion to proteins that
enhance solubility, such as NusA and thioredoxin (Trx), and epitope
tags, such as 6X His and S-Tag.TM. that aid purification and
detection of the recombinant protein. For example, constructs are
made utilizing pET NusA fusion system 43.1 such that regions of the
151P3D4 protein are expressed as amino-terminal fusions to
NusA.
[0475] C. Yeast Constructs:
[0476] pESC Constructs: To express 151P3D4 in the yeast species
Saccharomyces cerevisiae for generation of recombinant protein and
functional studies, all or parts of the 151P3D4 cDNA protein coding
sequence are cloned into the pESC family of vectors each of which
contain 1 of 4 selectable markers, HIS3, TRP1, LEU2, and URA3
(Stratagene, La Jolla, Calif.). These vectors allow controlled
expression from the same plasmid of up to 2 different genes or
cloned sequences containing either Flag.TM. or Myc epitope tags in
the same yeast cell. This system is useful to confirm
protein-protein interactions of 151P3D4. In addition, expression in
yeast yields similar post-translational modifications, such as
glycosylations and phosphorylations, that are found when expressed
in eukaryotic cells.
[0477] pESP Constructs: To express 151P3D4 in the yeast species
Saccharomyces pombe, all or parts of the 151P3D4 cDNA protein
coding sequence are cloned into the pESP family of vectors. These
vectors allow controlled high level of expression of a 151P3D4
protein sequence that is fused at either the amino terminus or at
the carboxyl terminus to GST which aids purification of the
recombinant protein. A Flag.TM. epitope tag allows detection of the
recombinant protein with anti-Flag.TM. antibody.
Example 8
[0478] Production of Recombinant 151P3D4 in Eukaryotic Systems
[0479] A. Mammalian Constructs:
[0480] To express recombinant 151P3D4 in eukaryotic cells, the full
or partial length 151P3D4 cDNA sequences can be cloned into any one
of a variety of expression vectors known in the art. One or more of
the following regions of 151P3D4 are expressed in these constructs,
amino acids 1 to 354 of 151P3D4 v.1, amino acids 1 to 721 of
151P3D4v.2, or any 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,
20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36,
37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 or more
contiguous amino acids from 151P3D4, variants, or analogs thereof.
In certain embodiments a region of a specific variant of 151P3D4 is
expressed that encodes an amino acid at a specific position which
differs from the amino acid of any other variant found at that
position. In other embodiments, a region of a variant of 151P3D4 is
expressed that lies partly or entirely within a sequence that is
unique to that variant.
[0481] The constructs can be transfected into any one of a wide
variety of mammalian cells such as 293T cells. Transfected 293T
cell lysates can be probed with the anti-151P3D4 polyclonal serum,
described herein.
[0482] pcDNA4/HisMax Constructs: To express 151P3D4 in mammalian
cells, a 151P3D4 ORF, or portions thereof, of 151P3D4 are cloned
into pcDNA4/HisMax Version A (Invitrogen, Carlsbad, Calif.).
Protein expression is driven from the cytomegalovirus (CMV)
promoter and the SP16 translational enhancer. The recombinant
protein has Xpress.TM. and six histidine (6X His) epitopes fused to
the amino-terminus. The pcDNA4/HisMax vector also contains the
bovine growth hormone (BGH) polyadenylation signal and
transcription termination sequence to enhance mRNA stability along
with the SV40 origin for episomal replication and simple vector
rescue in cell lines expressing the large T antigen. The Zeocin
resistance gene allows for selection of mammalian cells expressing
the protein and the ampicillin resistance gene and ColE1 origin
permits selection and maintenance of the plasmid in E. coli.
[0483] DcDNA3.1/MycHis Constructs: To express 151P3D4 in mammalian
cells, a 151P3D4 ORF, or portions thereof, of 151P3D4 with a
consensus Kozak translation initiation site was cloned into
pcDNA3.1/MycHis Version A (Invitrogen, Carlsbad, Calif.). Protein
expression is driven from the cytomegalovirus (CMV) promoter. The
recombinant protein has the myc epitope and 6X His epitope fused to
the carboxyl-terminus. The pcDNA3.1/MycHis vector also contains the
bovine growth hormone (BGH) polyadenylation signal and
transcription termination sequence to enhance mRNA stability, along
with the SV40 origin for episomal replication and simple vector
rescue in cell lines expressing the large T antigen. The Neomycin
resistance gene was used, as it allows for selection of mammalian
cells expressing the protein and the ampicillin resistance gene and
ColEI origin permits selection and maintenance of the plasmid in E.
coli. Results of expression from 151P3D4.pcDNA3.1/MycHis construct
are shown in FIG. 20.
[0484] PcDNA3.1/CT-GFP-TOPO Construct: To express 151P3D4 in
mammalian cells and to allow detection of the recombinant proteins
using fluorescence, a 151P3D4 ORF, or portions thereof, with a
consensus Kozak translation initiation site are cloned into
pcDNA3.1/CT-GFP-TOPO (Invitrogen, Calif.). Protein expression is
driven from the cytomegalovirus (CMV) promoter. The recombinant
proteins have the Green Fluorescent Protein (GFP) fused to the
carboxyl-terminus facilitating non-invasive, in vivo detection and
cell biology studies. The pcDNA3.1CT-GFP-TOPO vector also contains
the bovine growth hormone (BGH) polyadenylation signal and
transcription termination sequence to enhance mRNA stability along
with the SV40 origin for episomal replication and simple vector
rescue in cell lines expressing the large T antigen. The Neomycin
resistance gene allows for selection of mammalian cells that
express the protein, and the ampicillin resistance gene and ColE1
origin permits selection and maintenance of the plasmid in E. coli.
Additional constructs with an amino-terminal GFP fusion are made in
pcDNA3.1/NT-GFP-TOPO spanning the entire length of a 151P3D4
protein.
[0485] PAPtag: A 151P3D4 ORF, or portions thereof, is cloned into
pAPtag-5 (GenHunter Corp. Nashville, Tenn.). This construct
generates an alkaline phosphatase fusion at the carboxyl-terminus
of a 151P3D4 protein while fusing the IgG.kappa. signal sequence to
the amino-terminus. Constructs are also generated in which alkaline
phosphatase with an amino-terminal IgG.kappa. signal sequence is
fused to the amino-terminus of a 151P3D4 protein. The resulting
recombinant 151P3D4 proteins are optimized for secretion into the
media of transfected mammalian cells and can be used to identify
proteins such as ligands or receptors that interact with 151P3D4
proteins. Protein expression is driven from the CMV promoter and
the recombinant proteins also contain myc and 6X His epitopes fused
at the carboxyl-terminus that facilitates detection and
purification. The Zeocin resistance gene present in the vector
allows for selection of mammalian cells expressing the recombinant
protein and the ampicillin resistance gene permits selection of the
plasmid in E. coli.
[0486] ptag5: A 151P3D4 ORF, or portions thereof, is cloned into
pTag-5. This vector is similar to pAPtag but without the alkaline
phosphatase fusion. This construct generates 151P3D4 protein with
an amino-terminal IgG.kappa. signal sequence and myc and 6X His
epitope tags at the carboxyl-terminus that facilitate detection and
affinity purification. The resulting recombinant 151P3D4 protein is
optimized for secretion into the media of transfected mammalian
cells, and is used as immunogen or ligand to identify proteins such
as ligands or receptors that interact with the 151P3D4 proteins.
Protein expression is driven from the CMV promoter. The Zeocin
resistance gene present in the vector allows for selection of
mammalian cells expressing the protein, and the ampicillin
resistance gene permits selection of the plasmid in E. coli.
[0487] PsecFc: A 151P3D4 ORF, or portions thereof, is also cloned
into psecFc. The psecFc vector was assembled by cloning the human
immunoglobulin G1 (IgG) Fc (hinge, CH2, CH3 regions) into pSecTag2
(Invitrogen, Calif.). This construct generates an IgG1 Fc fusion at
the carboxyl-terminus of the 151P3D4 proteins, while fusing the
IgGK signal sequence to N-terminus. 151P3D4 fusions utilizing the
murine IgG1 Fc region are also used. The resulting recombinant
151P3D4 proteins are optimized for secretion into the media of
transfected mammalian cells, and can be used as immunogens or to
identify proteins such as ligands or receptors that interact with
151P3D4 protein. Protein expression is driven from the CMV
promoter. The hygromycin resistance gene present in the vector
allows for selection of mammalian cells that express the
recombinant protein, and the ampicillin resistance gene permits
selection of the plasmid in E. coli.
[0488] pSR.alpha. Constructs: To generate mammalian cell lines that
express 151P3D4 constitutively, 151P3D4 ORF, or portions thereof,
of 151P3D4 are cloned into pSR.alpha. constructs. Amphotropic and
ecotropic retroviruses are generated by transfection of pSR.alpha.
constructs into the 293T-10A1 packaging line or co-transfection of
pSR.alpha. and a helper plasmid (containing deleted packaging
sequences) into the 293 cells, respectively. The retrovirus is used
to infect a variety of mammalian cell lines, resulting in the
integration of the cloned gene, 151P3D4, into the host cell-lines.
Protein expression is driven from a long terminal repeat (LTR). The
Neomycin resistance gene present in the vector allows for selection
of mammalian cells that express the protein, and the ampicillin
resistance gene and ColE1 origin permit selection and maintenance
of the plasmid in E. coli. The retroviral vectors can thereafter be
used for infection and generation of various cell lines using, for
example, PC3, NIH 3T3, TsuPr1, 293 or rat-1 cells.
[0489] Additional pSR.alpha. constructs are made that fuse an
epitope tag such as the FLAG.TM. tag to the carboxyl-terminus of
151P3D4 sequences to allow detection using anti-Flag antibodies.
For example, the FLAG.TM. sequence 5' gat tac aag gat gac gac gat
aag 3' (SEQ ID NO:______) is added to cloning primer at the 3' end
of the ORF. Additional pSR.alpha. constructs are made to produce
both amino-terminal and carboxyl-terminal GFP and myc/6X His fusion
proteins of the full-length 151P3D4 proteins.
[0490] Additional Viral Vectors: Additional constructs are made for
viral-mediated delivery and expression of 151P3D4. High virus titer
leading to high level expression of 151P3D4 is achieved in viral
delivery systems such as adenoviral vectors and herpes amplicon
vectors. A 151P3D4 coding sequences or fragments thereof are
amplified by PCR and subcloned into the AdEasy shuttle vector
(Stratagene). Recombination and virus packaging are performed
according to the manufacturer's instructions to generate adenoviral
vectors. Alternatively, 151P3D4 coding sequences or fragments
thereof are cloned into the HSV-1 vector (Imgenex) to generate
herpes viral vectors. The viral vectors are thereafter used for
infection of various cell lines such as PC3, NIH 3T3, 293 or rat-1
cells.
[0491] Regulated Expression Systems: To control expression of
151P3D4 in mammalian cells, coding sequences of 151P3D4, or
portions thereof, are cloned into regulated mammalian expression
systems such as the T-Rex System (Invitrogen), the GeneSwitch
System (Invitrogen) and the tightly-regulated Ecdysone System
(Sratagene). These systems allow the study of the temporal and
concentration dependent effects of recombinant 151P3D4. These
vectors are thereafter used to control expression of 151P3D4 in
various cell lines such as PC3, NIH 3T3, 293 or rat-1 cells.
[0492] B. Baculovirus Expression Systems
[0493] To generate recombinant 151P3D4 proteins in a baculovirus
expression system, 151P3D4 ORF, or portions thereof, are cloned
into the baculovirus transfer vector pBlueBac 4.5 (Invitrogen),
which provides a His-tag at the N-terminus. Specifically,
pBlueBac-151P3D4 is co-transfected with helper plasmid pBac-N-Blue
(Invitrogen) into SF9 (Spodoptera frugiperda) insect cells to
generate recombinant baculovirus (see Invitrogen instruction manual
for details). Baculovirus is then collected from cell supernatant
and purified by plaque assay.
[0494] Recombinant 151P3D4 protein is then generated by infection
of HighFive insect cells (Invitrogen) with purified baculovirus.
Recombinant 151P3D4 protein can be detected using anti-151P3D4 or
anti-His-tag antibody. 151P3D4 protein can be purified and used in
various cell-based assays or as immunogen to generate polyclonal
and monoclonal antibodies specific for 151P3D4.
Example 9
[0495] Antigenicity Profiles and Secondary Structure
[0496] FIGS. 5(A & B), FIGS. 6(A & B), FIGS. 7(A & B),
FIGS. 8(A & B), and FIGS. 9(A & B) depict graphically five
amino acid profiles of 151P3D4 variants 1 and 2, each assessment
available by accessing the ProtScale website (URL
www.expasy.ch/cgi-bin/protscale.pl) on the ExPasy molecular biology
server.
[0497] These profiles: FIG. 5, Hydrophilicity, (Hopp T. P., Woods
K. R., 1981. Proc. Natl. Acad. Sci. U.S.A. 78:3824-3828); FIG. 6,
Hydropathicity, (Kyte J., Doolittle R. F., 1982. J. Mol. Biol.
157:105-132); FIG. 7, Percentage Accessible Residues (Janin J.,
1979 Nature 277:491-492); FIG. 8, Average Flexibility, (Bhaskaran
R., and Ponnuswamy P. K., 1988. Int. J. Pept. Protein Res.
32:242-255); FIG. 9, Beta-turn (Deleage, G., Roux B. 1987 Protein
Engineering 1:289-294); and optionally others available in the art,
such as on the ProtScale website, were used to identify antigenic
regions of the 151P3D4 protein. Each of the above amino acid
profiles of 151P3D4 were generated using the following ProtScale
parameters for analysis: 1) A window size of 9; 2) 100% weight of
the window edges compared to the window center; and, 3) amino acid
profile values normalized to lie between 0 and 1.
[0498] Hydrophilicity (FIG. 5), Hydropathicity (FIG. 6) and
Percentage Accessible Residues (FIG. 7) profiles were used to
determine stretches of hydrophilic amino acids (i.e., values
greater than 0.5 on the Hydrophilicity and Percentage Accessible
Residues profile, and values less than 0.5 on the Hydropathicity
profile). Such regions are likely to be exposed to the aqueous
environment, be present on the surface of the protein, and thus
available for immune recognition, such as by antibodies.
[0499] Average Flexibility (FIG. 8) and Beta-turn (FIG. 9) profiles
determine stretches of amino acids (i.e., values greater than 0.5
on the Beta-turn profile and the Average Flexibility profile) that
are not constrained in secondary structures such as beta sheets and
alpha helices. Such regions are also more likely to be exposed on
the protein and thus accessible to immune recognition, such as by
antibodies.
[0500] Antigenic sequences of the 151P3D4 variant proteins
indicated, e.g., by the profiles set forth in FIGS. 5(A & B),
FIGS. 6(A & B), FIGS. 7(A & B), FIGS. 8(A & B), and/or
FIGS. 9(A & B) are used to prepare immunogens, either peptides
or nucleic acids that encode them, to generate therapeutic and
diagnostic anti-151P3D4 antibodies. The immunogen can be any 5, 6,
7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 30, 35, 40, 45, 50 or more than 50 contiguous amino acids,
or the corresponding nucleic acids that encode them, from the
151P3D4 protein variants 1 and 2 listed in FIGS. 2 and 3. In
particular, peptide immunogens of the invention can comprise, a
peptide region of at least 5 amino acids of FIGS. 2 and 3 in any
whole number increment that includes an amino acid position having
a value greater than 0.5 in the Hydrophilicity profiles of FIG. 5;
a peptide region of at least 5 amino acids of FIGS. 2 and 3 in any
whole number increment that includes an amino acid position having
a value less than 0.5 in the Hydropathicity profile of FIG. 6; a
peptide region of at least 5 amino acids of FIGS. 2 and 3 in any
whole number increment that includes an amino acid position having
a value greater than 0.5 in the Percent Accessible Residues
profiles of FIG. 7; a peptide region of at least 5 amino acids of
FIGS. 2 and 3 in any whole number increment that includes an amino
acid position having a value greater than 0.5 in the Average
Flexibility profiles on FIG. 8; and, a peptide region of at least 5
amino acids of FIGS. 2 and 3 in any whole number increment that
includes an amino acid position having a value greater than 0.5 in
the Beta-turn profile of FIGS. 9. Peptide immunogens of the
invention can also comprise nucleic acids that encode any of the
forgoing.
[0501] All immunogens of the invention, peptide or nucleic acid,
can be embodied in human unit dose form, or comprised by a
composition that includes a pharmaceutical excipient compatible
with human physiology.
[0502] The secondary structure of 151P3D4 protein variants 1 and 2,
namely the predicted presence and location of alpha helices,
extended strands, and random coils, is predicted from the primary
amino acid sequence using the HNN--Hierarchical Neural Network
method (Guermeur, 1997, http://pbil.ibcp.fr/cgi-bin/npsa_automat.pl
1?page=npsa_nn.html), accessed from the ExPasy molecular biology
server (http://www.expasy.ch/t- ools/). The analysis indicates that
151P3D4 variant 1 is composed of 25.71% alpha helix, 21.47%
extended strand, and 52.82% random coil (FIG. 13A). Variant 2 is
composed of 25.80% alpha helix, 16.64% extended strand, and 57.56%
random coil (FIG. 13B).
[0503] Analysis for the potential presence of transmembrane domains
in the 151P3D4 variant proteins was carried out using a variety of
transmembrane prediction algorithms accessed from the ExPasy
molecular biology server (http://www.expasy.ch/tools/). The
programs do not predict the presence of transmembrane domains in
the 151P3D4 protein variants, suggesting that they are soluble
proteins.
Example 10
[0504] Generation of 151P3D4 Polyclonal Antibodies
[0505] Polyclonal antibodies can be raised in a mammal, for
example, by one or more injections of an immunizing agent and, if
desired, an adjuvant. Typically, the immunizing agent and/or
adjuvant will be injected in the mammal by multiple subcutaneous or
intraperitoneal injections. In addition to immunizing with a full
length 151P3D4 protein variant, computer algorithms are employed in
design of immunogens that, based on amino acid sequence analysis
contain characteristics of being antigenic and available for
recognition by the immune system of the immunized host (see the
Example entitled "Antigenicity Profiles"). Such regions would be
predicted to be hydrophilic, flexible, in beta-turn conformations,
and be exposed on the surface of the protein (see, e.g., FIGS. 5(A
& B), FIGS. 6(A & B), FIGS. 7(A & B), FIGS. 8(A &
B), or FIGS. 9(A & B) for amino acid profiles that indicate
such regions of 151P3D4 protein variants).
[0506] For example, recombinant bacterial fusion proteins or
peptides containing hydrophilic, flexible, beta-turn regions of
151P3D4 protein variants are used as antigens to generate
polyclonal antibodies in New Zealand White rabbits. For example, in
151P3D4 variant 1, such regions include, but are not limited to,
amino acids 99-151, amino acids 218-249, and amino acids 311-332.
In sequence specific for variant 2, such regions include, but are
not limited to, amino acids 16-38, amino acids 76-90, amino acids
182-230, and amino acids 383-400. It is useful to conjugate the
immunizing agent to a protein known to be immunogenic in the mammal
being immunized. Examples of such immunogenic proteins include, but
are not limited to, keyhole limpet hemocyanin (KLH), serum albumin,
bovine thyroglobulin, and soybean trypsin inhibitor. In one
embodiment, a peptide encoding amino acids 311-332 of 151P3D4
variant 1 is conjugated to KLH and used to immunize the rabbit.
Alternatively the immunizing agent may include all or portions of
the 151P3D4 variant proteins, analogs or fusion proteins thereof.
For example, the 151P3D4 variant 1 amino acid sequence can be fused
using recombinant DNA techniques to any one of a variety of fusion
protein partners that are well known in the art, such as
glutathione-S-transferase (GST) and HIS tagged fusion proteins.
Such fusion proteins are purified from induced bacteria using the
appropriate affinity matrix.
[0507] In one embodiment, a GST-fusion protein encoding the
N-terminal region of 151P3D4 variant 1, amino acids 16-150, minus
the first 15 amino acids that likely encodes a cleavable signal
peptide, is produced and purified and used as immunogen. Other
recombinant bacterial fusion proteins that may be employed include
maltose binding protein, LacZ, thioredoxin, NusA, or an
immunoglobulin constant region (see the section entitled
"Production of 151P3D4 in Prokaryotic Systems" and Current
Protocols In Molecular Biology, Volume 2, Unit 16, Frederick M.
Ausubul et al. eds., 1995; Linsley, P. S., Brady, W., Urnes, M.,
Grosmaire, L., Damle, N., and Ledbetter, L.(1991) J.Exp. Med. 174,
561-566).
[0508] In addition to bacterial derived fusion proteins, mammalian
expressed protein antigens are also used. These antigens are
expressed from mammalian expression vectors such as the Tag5 and
Fc-fusion vectors (see the section entitled "Production of
Recombinant 151P3D4 in Eukaryotic Systems"), and retain
post-translational modifications such as glycosylations found in
native protein. In one embodiment, amino acids 16-354 of variant 1,
minus the endogenous signal peptide, is cloned into the Tag5
mammalian secretion vector. The recombinant protein is purified by
metal chelate chromatography from tissue culture supernatants of
293T cells stably expressing the recombinant vector. The purified
Tag5 151P3D4 protein is then used as immunogen.
[0509] During the immunization protocol, it is useful to mix or
emulsify the antigen in adjuvants that enhance the immune response
of the host animal. Examples of adjuvants include, but are not
limited to, complete Freund's adjuvant (CFA) and MPL-TDM adjuvant
(monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).
[0510] In a typical protocol, rabbits are initially immunized
subcutaneously with up to 200 .mu.g, typically 100-200 .mu.g, of
fusion protein or peptide conjugated to KLH mixed in complete
Freund's adjuvant (CFA). Rabbits are then injected subcutaneously
every two weeks with up to 200 .mu.g, typically 100-200 .mu.g, of
the immunogen in incomplete Freund's adjuvant (IFA). Test bleeds
are taken approximately 7-10 days following each immunization and
used to monitor the titer of the antiserum by ELISA.
[0511] To test reactivity and specificity of immune serum, such as
the rabbit serum derived from immunization with the Tag5-151P3D4
variant 1 protein, the full-length 151P3D4 variant 1 cDNA is cloned
into pCDNA 3.1 myc-his expression vector (Invitrogen, see the
Example entitled "Production of Recombinant 151P3D4 in Eukaryotic
Systems"). After transfection of the constructs into 293T cells,
cell lysates are probed with the anti-151P3D4 serum and with
anti-His antibody (Santa Cruz Biotechnologies, Santa Cruz, Calif.)
to determine specific reactivity to denatured 151P3D4 protein using
the Western blot technique (FIG. 20) shows expression of Myc His
epitope tagged 151P3D4 variant 1 protein in 293T cells as detected
by an anti-His antibody. In addition, the immune serum is tested by
fluorescence microscopy, flow cytometry and immunoprecipitation
against 293T and other recombinant 151P3D4-expressing cells to
determine specific recognition of native protein. Western blot,
immunoprecipitation, fluorescent microscopy, and flow cytometric
techniques using cells that endogenously express 151P3D4 are also
carried out to test reactivity and specificity.
[0512] Anti-serum from rabbits immunized with 151P3D4 variant
fusion proteins, such as GST and MBP fusion proteins, are purified
by depletion of antibodies reactive to the fusion partner sequence
by passage over an affinity column containing the fusion partner
either alone or in the context of an irrelevant fusion protein. For
example, antiserum derived from a GST-151P3D4 variant 1 fusion
protein encoding amino acids 16-150 is first purified by passage
over a column of GST protein covalently coupled to AffiGel matrix
(BioRad, Hercules, Calif.). The antiserum is then affinity purified
by passage over a column composed of a MBP-fusion protein also
encoding amino acids 16-150 covalently coupled to AffiGel matrix.
The serum is then further purified by protein G affinity
chromatography to isolate the IgG fraction. Sera from other
His-tagged antigens and peptide immunized rabbits as well as fusion
partner depleted sera are affinity purified by passage over a
column matrix composed of the original protein immunogen or free
peptide.
Example 11
[0513] Generation of 151P3D4 Monoclonal Antibodies (mAbs)
[0514] In one embodiment, therapeutic mAbs to 151P3D4 variants
comprise those that react with epitopes specific for each variant
protein or specific to sequences in common between the variants
that would disrupt or modulate the biological function of the
151P3D4 variants, for example those that would disrupt the
interaction with ligands and binding partners. Immunogens for
generation of such mAbs include those designed to encode or contain
the entire 151P3D4 protein variant sequence, regions of the 151P3D4
protein variants predicted to be antigenic from computer analysis
of the amino acid sequence (see, e.g., FIGS. 5(A & B), FIGS.
6(A & B), FIGS. 7(A & B), FIGS. 8(A & B), or FIGS. 9(A
& B), and the Example entitled "Antigenicity Profiles").
Immunogens include peptides, recombinant bacterial proteins, and
mammalian expressed Tag 5 proteins and human and murine IgG FC
fusion proteins. In addition, cells engineered to express high
levels of a respective 151P3D4 variant, such as 293T-151P3D4
variant 1 or 300.19-151P3D4 variant lmurine Pre-B cells, are used
to immunize mice.
[0515] To generate mAbs to a 151P3D4 variant, mice are first
immunized intraperitoneally (IP) with, typically, 10-50 .mu.g of
protein immunogen or 10.sup.7 151P3D4-expressing cells mixed in
complete Freund's adjuvant. Mice are then subsequently immunized IP
every 2-4 weeks with, typically, 10-50 .mu.g of protein immunogen
or 10.sup.7 cells mixed in incomplete Freund's adjuvant.
Alternatively, MPL-TDM adjuvant is used in immunizations. In
addition to the above protein and cell-based immunization
strategies, a DNA-based immunization protocol is employed in which
a mammalian expression vector encoding a 151P3D4 variant sequence
is used to immunize mice by direct injection of the plasmid DNA.
For example, amino acids 16-354 is cloned into the Tag5 mammalian
secretion vector and the recombinant vector is used as immunogen.
In another example the same amino acids are cloned into an
Fc-fusion secretion vector in which the 151P3D4 variant 1 sequence
is fused at the amino-terminus to an IgK leader sequence and at the
carboxyl-terminus to the coding sequence of the human or murine IgG
Fc region. This recombinant vector is then used as immunogen. The
plasmid immunization protocols are used in combination with
purified proteins expressed from the same vector and with cells
expressing the respective 151P3D4 variant.
[0516] During the immunization protocol, test bleeds are taken 7-10
days following an injection to monitor titer and specificity of the
immune response. Once appropriate reactivity and specificity is
obtained as determined by ELISA, Western blotting,
immunoprecipitation, fluorescence microscopy, and flow cytometric
analyses, fusion and hybridoma generation is then carried out with
established procedures well known in the art (see, e.g., Harlow and
Lane, 1988).
[0517] In one embodiment for generating 151P3D4 monoclonal
antibodies, a Tag5-151P3D4 variant 1 antigen encoding amino acids
16-354, is expressed and purified from stably transfected 293T
cells. Balb C mice are initially immunized intraperitoneally with
25 .mu.g of the Tag5-151P3D4 variant 1 protein mixed in complete
Freund's adjuvant. Mice are subsequently immunized every two weeks
with 25 .mu.g of the antigen mixed in incomplete Freund's adjuvant
for a total of three immunizations. ELISA using the Tag5 antigen
determines the titer of serum from immunized mice. Reactivity and
specificity of serum to full length 151P3D4 variant 1 protein is
monitored by Western blotting, immunoprecipitation and flow
cytometry using 293T cells transfected with an expression vector
encoding the 151P3D4 variant 1 cDNA (see e.g., the Example entitled
"Production of Recombinant 151P3D4 in Eukaryotic Systems" and FIG.
20. Other recombinant 151P3D4 variant 1-expressing cells or cells
endogenously expressing 151P3D4 variant 1 are also used. Mice
showing the strongest reactivity are rested and given a final
injection of Tag5 antigen in PBS and then sacrificed four days
later. The spleens of the sacrificed mice are harvested and fused
to SPO/2 myeloma cells using standard procedures (Harlow and Lane,
1988). Supernatants from HAT selected growth wells are screened by
ELISA, Western blot, immunoprecipitation, fluorescent microscopy,
and flow cytometry to identify 151P3D4 specific antibody-producing
clones.
[0518] In another embodiment, a Tag5 antigen encoding amino acids
1-400 of variant 2 is produced, purified and used as immunogen to
derive monoclonal antibodies specific to 151P3D4 variant 2.
Hybridoma supernatants are then screened on both 151P3D4 variant 2-
and 151P3D4 variant 1-expressing cells to identify specific
anti-151P3D4 variant 2 monoclonal antibodies.
[0519] The binding affinity of a 151P3D4 monoclonal antibody is
determined using standard technologies. Affinity measurements
quantify the strength of antibody to epitope binding and are used
to help define which 151P3D4 monoclonal antibodies preferred for
diagnostic or therapeutic use, as appreciated by one of skill in
the art. The BIAcore system (Uppsala, Sweden) is a preferred method
for determining binding affinity. The BIAcore system uses surface
plasmon resonance (SPR, Welford K. 1991, Opt. Quant. Elect. 23:1;
Morton and Myszka, 1998, Methods in Enzymology 295: 268) to monitor
biomolecular interactions in real time. BIAcore analysis
conveniently generates association rate constants, dissociation
rate constants, equilibrium dissociation constants, and affinity
constants.
Example 12
[0520] HLA Class I and Class II Binding Assays
[0521] HLA class I and class II binding assays using purified HLA
molecules are performed in accordance with disclosed protocols
(e.g., PCT publications WO 94/20127 and WO 94/03205; Sidney et al.,
Current Protocols in Immunology 18.3.1 (1998); Sidney, et al., J.
Immunol. 154:247 (1995); Sette, et al., Mol. Immunol. 31:813
(1994)). Briefly, purified MHC molecules (5 to 500 nM) are
incubated with various unlabeled peptide inhibitors and 1-10 nM
.sup.125I-radiolabeled probe peptides as described. Following
incubation, MHC-peptide complexes are separated from free peptide
by gel filtration and the fraction of peptide bound is determined.
Typically, in preliminary experiments, each MHC preparation is
titered in the presence of fixed amounts of radiolabeled peptides
to determine the concentration of HLA molecules necessary to bind
10-20% of the total radioactivity. All subsequent inhibition and
direct binding assays are performed using these HLA
concentrations.
[0522] Since under these conditions [label]<[HLA] and
IC.sub.50.gtoreq.[HLA], the measured IC.sub.50 values are
reasonable approximations of the true K.sub.D values. Peptide
inhibitors are typically tested at concentrations ranging from 120
.mu.g/ml to 1.2 ng/ml, and are tested in two to four completely
independent experiments. To allow comparison of the data obtained
in different experiments, a relative binding figure is calculated
for each peptide by dividing the IC.sub.50 of a positive control
for inhibition by the IC.sub.50 for each tested peptide (typically
unlabeled versions of the radiolabeled probe peptide). For database
purposes, and inter-experiment comparisons, relative binding values
are compiled. These values can subsequently be converted back into
IC.sub.50 nM values by dividing the IC.sub.50 nM of the positive
controls for inhibition by the relative binding of the peptide of
interest. This method of data compilation is accurate and
consistent for comparing peptides that have been tested on
different days, or with different lots of purified MHC.
[0523] Binding assays as outlined above may be used to analyze HLA
supermotif and/or HLA motif-bearing peptides (see Table IV).
Example 13
[0524] Identification of HLA Supermotif- and Motif-Bearing CTL
Candidate Epitopes
[0525] HLA vaccine compositions of the invention can include
multiple epitopes. The multiple epitopes can comprise multiple HLA
supermotifs or motifs to achieve broad population coverage. This
example illustrates the identification and confirmation of
supermotif- and motif-bearing epitopes for the inclusion in such a
vaccine composition. Calculation of population coverage is
performed using the strategy described below.
[0526] Computer Searches and Algorithms for Identification of
Supermotif and/or Motif-Bearing Epitopes
[0527] The searches performed to identify the motif-bearing peptide
sequences in the Example entitled "Antigenicity Profiles" and
Tables V-XVIII and XXII-LI employ the protein sequence data from
the gene product of 151P3D4 set forth in FIGS. 2 and 3.
[0528] Computer searches for epitopes bearing HLA Class I or Class
II supermotifs or motifs are performed as follows. All translated
151P3D4 protein sequences are analyzed using a-text string search
software program to identify potential peptide sequences containing
appropriate HLA binding motifs; such programs are readily produced
in accordance with information in the art in view of known
motif/supermotif disclosures. Furthermore, such calculations can be
made mentally.
[0529] Identified A2-, A3-, and DR-supermotif sequences are scored
using polynomial algorithms to predict their capacity to bind to
specific HLA-Class I or Class II molecules. These polynomial
algorithms account for the impact of different amino acids at
different positions, and are essentially based on the premise that
the overall affinity (or .DELTA.G) of peptide-HLA molecule
interactions can be approximated as a linear polynomial function of
the type:
".DELTA.G"=a.sub.1i.times.a.sub.2i.times.a.sub.3i . . .
.times.a.sub.ni
[0530] where a.sub.ji is a coefficient which represents the effect
of the presence of a given amino acid (j) at a given position (i)
along the sequence of a peptide of n amino acids. The crucial
assumption of this method is that the effects at each position are
essentially independent of each other (i.e., independent binding of
individual side-chains). When residue j occurs at position i in the
peptide, it is assumed to contribute a constant amount j.sub.i to
the free energy of binding of the peptide irrespective of the
sequence of the rest of the peptide.
[0531] The method of derivation of specific algorithm coefficients
has been described in Gulukota et al., J. Mol. Biol. 267:1258-126,
1997; (see also Sidney et al., Human Immunol. 45:79-93, 1996; and
Southwood et al., J. Immunol. 160:3363-3373, 1998). Briefly, for
all i positions, anchor and non-anchor alike, the geometric mean of
the average relative binding (ARB) of all peptides carrying j is
calculated relative to the remainder of the group, and used as the
estimate of j.sub.i. For Class II peptides, if multiple alignments
are possible, only the highest scoring alignment is utilized,
following an iterative procedure. To calculate an algorithm score
of a given peptide in a test set, the ARB values corresponding to
the sequence of the peptide are multiplied. If this product exceeds
a chosen threshold, the peptide is predicted to bind. Appropriate
thresholds are chosen as a function of the degree of stringency of
prediction desired.
[0532] Selection of HLA-A2 Supertype Cross-Reactive Peptides
[0533] Protein sequences from 151P3D4 are scanned utilizing motif
identification software, to identify 8-, 9- 10- and 11-mer
sequences containing the HLA-A2-supermotif main anchor specificity.
Typically, these sequences are then scored using the protocol
described above and the peptides corresponding to the
positive-scoring sequences are synthesized and tested for their
capacity to bind purified HLA-A*0201 molecules in vitro (HLA-A*0201
is considered a prototype A2 supertype molecule).
[0534] These peptides are then tested for the capacity to bind to
additional A2-supertype molecules (A*0202, A*0203, A*0206, and
A*6802). Peptides that bind to at least three of the five
A2-supertype alleles tested are typically deemed A2-supertype
cross-reactive binders. Preferred peptides bind at an affinity
equal to or less than 500 nM to three or more HLA-A2 supertype
molecules.
[0535] Selection of HLA-A3 Supermotif-Bearing Epitopes
[0536] The 151P3D4 protein sequence(s) scanned above is also
examined for the presence of peptides with the HLA-A3-supermotif
primary anchors. Peptides corresponding to the HLA A3
supermotif-bearing sequences are then synthesized and tested for
binding to HLA-A*0301 and HLA-A*1101 molecules, the molecules
encoded by the two most prevalent A3-supertype alleles. The
peptides that bind at least one of the two alleles with binding
affinities of .ltoreq.500 nM, often .ltoreq.200 nM, are then tested
for binding cross-reactivity to the other common A3-supertype
alleles (e.g., A*3101, A*3301, and A*6801) to identify those that
can bind at least three of the five HLA-A3-supertype molecules
tested.
[0537] Selection of HLA-B7 Supermotif Bearing Epitopes
[0538] The 151P3D4 protein(s) scanned above is also analyzed for
the presence of 8-, 9- 10-, or 11-mer peptides with the
HLA-B7-supermotif. Corresponding peptides are synthesized and
tested for binding to HLA-B*0702, the molecule encoded by the most
common B7-supertype allele (i.e., the prototype B7 supertype
allele). Peptides binding B*0702 with IC.sub.50 of .ltoreq.500 nM
are identified using standard methods. These peptides are then
tested for binding to other common B7-supertype molecules (e.g.,
B*3501, B*5101, B*5301, and B*5401). Peptides capable of binding to
three or more of the five B7-supertype alleles tested are thereby
identified.
[0539] Selection of A1 and A24 Motif-Bearing Epitopes
[0540] To further increase population coverage, HLA-A 1 and -A24
epitopes can also be incorporated into vaccine compositions. An
analysis of the 151P3D4 protein can also be performed to identify
HLA-A1- and A24-motif-containing sequences.
[0541] High affinity and/or cross-reactive binding epitopes that
bear other motif and/or supermotifs are identified using analogous
methodology.
Example 14
[0542] Confirmation of Immunogenicity
[0543] Cross-reactive candidate CTL A2-supermotif-bearing peptides
that are identified as described herein are selected to confirm in
vitro immunogenicity. Confirmation is performed using the following
methodology:
[0544] Target Cell Lines for Cellular Screening:
[0545] The .221A2.1 cell line, produced by transferring the
HLA-A2.1 gene into the HLA-A, -B, -C null mutant human
B-lymphoblastoid cell line 721.221, is used as the peptide-loaded
target to measure activity of HLA-A2.1-restricted CTL. This cell
line is grown in RPMI-1640 medium supplemented with antibiotics,
sodium pyruvate, nonessential amino acids and 10% (v/v) heat
inactivated FCS. Cells that express an antigen of interest, or
transfectants comprising the gene encoding the antigen of interest,
can be used as target cells to confirm the ability of
peptide-specific CTLs to recognize endogenous antigen.
[0546] Primary CTL Induction Cultures:
[0547] Generation of Dendritic Cells (DC): PBMCs are thawed in RPMI
with 30 .mu.g/ml DNAse, washed twice and resuspended in complete
medium (RPMI-1640 plus 5% AB human serum, non-essential amino
acids, sodium pyruvate, L-glutamine and penicillin/streptomycin).
The monocytes are purified by plating 10.times.10.sup.6 PBMC/well
in a 6-well plate. After 2 hours at 37.degree. C., the non-adherent
cells are removed by gently shaking the plates and aspirating the
supernatants. The wells are washed a total of three times with 3 ml
RPMI to remove most of the non-adherent and loosely adherent cells.
Three ml of complete medium containing 50 ng/ml of GM-CSF and 1,000
U/ml of IL-4 are then added to each well. TNF.alpha. is added to
the DCs on day 6 at 75 ng/ml and the cells are used for CTL
induction cultures on day 7.
[0548] Induction of CTL with DC and Peptide: CD8+ T-cells are
isolated by positive selection with Dynal immunomagnetic beads
(Dynabeads.RTM. M-450) and the detacha-bead.RTM. reagent. Typically
about 200-250.times.10.sup.6 PBMC are processed to obtain
24.times.10.sup.6 CD8.sup.+ T-cells (enough for a 48-well plate
culture). Briefly, the PBMCs are thawed in RPMI with 30 .mu.g/ml
DNAse, washed once with PBS containing 1% human AB serum and
resuspended in PBS/1% AB serum at a concentration of
20.times.10.sup.6cells/ml. The magnetic beads are washed 3 times
with PBS/AB serum, added to the cells (140 .mu.l
beads/20.times.10.sup.6 cells) and incubated for 1 hour at
4.degree. C. with continuous mixing. The beads and cells are washed
4.times. with PBS/AB serum to remove the nonadherent cells and
resuspended at 100.times.10.sup.6 cells/ml (based on the original
cell number) in PBS/AB serum containing 100 .mu.l/ml
detacha-bead.RTM. reagent and 30 .mu.g/ml DNAse. The mixture is
incubated for 1 hour at room temperature with continuous mixing.
The beads are washed again with PBS/AB/DNAse to collect the CD8+
T-cells. The DC are collected and centrifuged at 1300 rpm for 5-7
minutes, washed once with PBS with 1% BSA, counted and pulsed with
40 .mu.g/ml of peptide at a cell concentration of
1-2.times.10.sup.6/ml in the presence of 3 .mu.g/ml
.beta..sub.2-microglobulin for 4 hours at 20.degree. C. The DC are
then irradiated (4,200 rads), washed 1 time with medium and counted
again.
[0549] Setting up induction cultures: 0.25 ml cytokine-generated DC
(at .times.10.sup.5 cells/ml) are co-cultured with 0.25 ml of CD8+
T-cells (at 2.times.10.sup.6 cell/ml) in each well of a 48-well
plate in the presence of 10 ng/ml of IL-7. Recombinant human IL-10
is added the next day at a final concentration of 10 ng/ml and
rhuman IL-2 is added 48 hours later at 10 IU/ml.
[0550] Restimulation of the induction cultures with peptide-pulsed
adherent cells: Seven and fourteen days after the primary
induction, the cells are restimulated with peptide-pulsed adherent
cells. The PBMCs are thawed and washed twice with RPMI and DNAse.
The cells are resuspended at 5.times.10.sup.6 cells/ml and
irradiated at .about.4200 rads. The PBMCs are plated at
2.times.10.sup.6 in 0.5 ml complete medium per well and incubated
for 2 hours at 37.degree. C. The plates are washed twice with RPMI
by tapping the plate gently to remove the nonadherent cells and the
adherent cells pulsed with 10 .mu.g/ml of peptide in the presence
of 3 .mu.g/ml .beta..sub.2 microglobulin in 0.25 ml RPMI/5% AB per
well for 2 hours at 37.degree. C. Peptide solution from each well
is aspirated and the wells are washed once with RPMI. Most of the
media is aspirated from the induction cultures (CD8+ cells) and
brought to 0.5 ml with fresh media. The cells are then transferred
to the wells containing the peptide-pulsed adherent cells. Twenty
four hours later recombinant human IL-10 is added at a final
concentration of 10 ng/ml and recombinant human IL2 is added the
next day and again 2-3 days later at 50 IU/ml (Tsai et al.,
Critical Reviews in Immunology 18(1-2):65-75, 1998). Seven days
later, the cultures are assayed for CTL activity in a .sup.51Cr
release assay. In some experiments the cultures are assayed for
peptide-specific recognition in the in situ IFN.gamma. ELISA at the
time of the second restimulation followed by assay of endogenous
recognition 7 days later. After expansion, activity is measured in
both assays for a side-by-side comparison.
[0551] Measurement of CTL Lytic Activity by .sup.51Cr release.
[0552] Seven days after the second restimulation, cytotoxicity is
determined in a standard (5 hr) .sup.51Cr release assay by assaying
individual wells at a single E:T. Peptide-pulsed targets are
prepared by incubating the cells with 10 .mu.g/ml peptide overnight
at 37.degree. C.
[0553] Adherent target cells are removed from culture flasks with
trypsin-EDTA. Target cells are labeled with 200 .mu.Ci of .sup.51Cr
sodium chromate (Dupont, Wilmington, Del.) for1 hour at 37.degree.
C. Labeled target cells are resuspended at 10.sup.6 per ml and
diluted 1:10 with K562 cells at a concentration of
3.3.times.10.sup.6/ml (an NK-sensitive erythroblastoma cell line
used to reduce non-specific lysis). Target cells (100 .mu.l) and
effectors (1001 .mu.l) are plated in 96 well round-bottom plates
and incubated for 5 hours at 37.degree. C. At that time, 100 .mu.l
of supernatant are collected from each well and percent lysis is
determined according to the formula:
[(cpm of the test sample-cpm of the spontaneous .sup.51Cr release
sample)/(cpm of the maximal .sup.51Cr release sample-cpm of the
spontaneous .sup.51Cr release sample)].times.100.
[0554] Maximum and spontaneous release are determined by incubating
the labeled targets with 1% Triton X-100 and media alone,
respectively. A positive culture is defined as one in which the
specific lysis (sample-background) is 10% or higher in the case of
individual wells and is 15% or more at the two highest E:T ratios
when expanded cultures are assayed.
[0555] In situ Measurement of Human IFN.gamma. Production as an
Indicator of Peptide-Specific and Endogenous Recognition
[0556] Immulon 2 plates are coated with mouse anti-human IFN.gamma.
monoclonal antibody (4 .mu.g/ml 0.1M NaHCO.sub.3, pH8.2) overnight
at 4.degree. C. The plates are washed with Ca.sup.2+,
Mg.sup.2+-free PBS/0.05% Tween 20 and blocked with PBS/10% FCS for
two hours, after which the CTLs (100 .mu.l/well) and targets (100
.mu.l/well) are added to each well, leaving empty wells for the
standards and blanks (which received media only). The target cells,
either peptide-pulsed or endogenous targets, are used at a
concentration of 1.times.10.sup.6 cells/ml. The plates are
incubated for 48 hours at 37.degree. C. with 5% CO.sub.2.
[0557] Recombinant human IFN-gamma is added to the standard wells
starting at 400 pg or 120 pg/100 microliter/well and the plate
incubated for two hours at 37.degree. C. The plates are washed and
100 .mu.l of biotinylated mouse anti-human IFN-gamma monoclonal
antibody (2 microgram/ml in PBS/3% FCS/0.05% Tween 20) are added
and incubated for 2 hours at room temperature. After washing again,
100 microliter HRP-streptavidin (1:4000) are added and the plates
incubated for one hour at room temperature. The plates are then
washed 6.times. with wash buffer, 100 microliter/well developing
solution (TMB 1:1) are added, and the plates allowed to develop for
5-15 minutes. The reaction is stopped with 50 microliter/well 1M
H.sub.3PO.sub.4 and read at OD450. A culture is considered positive
if it measured at least 50 pg of IFN-gamma/well above background
and is twice the background level of expression.
[0558] CTL Expansion.
[0559] Those cultures that demonstrate specific lytic activity
against peptide-pulsed targets and/or tumor targets are expanded
over a two week period with anti-CD3. Briefly, 5.times.10.sup.4
CD8+ cells are added to a T25 flask containing the following:
1.times.10.sup.6 irradiated (4,200 rad) PBMC (autologous or
allogeneic) per ml, 2.times.10.sup.5 irradiated (8,000 rad)
EBV-transformed cells per ml, and OKT3 (anti-CD3) at 30 ng per ml
in RPMI-1640 containing 10% (v/v) human AB serum, non-essential
amino acids, sodium pyruvate, 25 .mu.M 2-mercaptoethanol,
L-glutamine and penicillin/streptomycin. Recombinant human IL2 is
added 24 hours later at a final concentration of 200 IU/ml and
every three days thereafter with fresh media at 50 IU/ml. The cells
are split if the cell concentration exceeds 1.times.10.sup.6/ml and
the cultures are assayed between days 13 and 15 at E:T ratios of
30, 10, 3 and 1:1 in the .sup.51Cr release assay or at
1.times.10.sup.6/ml in the in situ IFN.gamma. assay using the same
targets as before the expansion.
[0560] Cultures are expanded in the absence of anti-CD3.sup.+ as
follows. Those cultures that demonstrate specific lytic activity
against peptide and endogenous targets are selected and
5.times.10.sup.4 CD8.sup.+ cells are added to a T25 flask
containing the following: 1.times.10.sup.6 autologous PBMC per ml
which have been peptide-pulsed with 10 .mu.g/ml peptide for two
hours at 37.degree. C. and irradiated (4,200 rad); 2.times.10.sup.5
irradiated (8,000 rad) EBV-transformed cells per ml RPMI-1640
containing 10% (v/v) human AB serum, non-essential AA, sodium
pyruvate, 25 mM 2-ME, L-glutamine and gentamicin.
[0561] Immunogenicity of A2 Supermotif-Bearing Peptides
[0562] A2-supermotif cross-reactive binding peptides are tested in
the cellular assay for the ability to induce peptide-specific CTL
in normal individuals. In this analysis, a peptide is typically
considered to be an epitope if it induces peptide-specific CTLs in
at least individuals, and preferably, also recognizes the
endogenously expressed peptide.
[0563] Immunogenicity can also be confirmed using PBMCs isolated
from patients bearing a tumor that expresses 151P3D4. Briefly,
PBMCs are isolated from patients, re-stimulated with peptide-pulsed
monocytes and assayed for the ability to recognize peptide-pulsed
target cells as well as transfected cells endogenously expressing
the antigen.
[0564] Evaluation of A*03/A11 Immunogenicity
[0565] HLA-A3 supermotif-bearing cross-reactive binding peptides
are also evaluated for immunogenicity using methodology analogous
for that used to evaluate the immunogenicity of the HLA-A2
supermotif peptides.
[0566] Evaluation of B7 Immunogenicity
[0567] Immunogenicity screening of the B7-supertype cross-reactive
binding peptides identified as set forth herein are confirmed in a
manner analogous to the confirmation of A2-and
A3-supermotif-bearing peptides.
[0568] Peptides bearing other supermotifs/motifs, e.g., HLA-A1,
HLA-A24 etc. are also confirmed using similar methodology
Example 15
[0569] Implementation of the Extended Supermotif to Improve the
Binding Capacity of Native Epitopes by Creating Analogs
[0570] HLA motifs and supermotifs (comprising primary and/or
secondary residues) are useful in the identification and
preparation of highly cross-reactive native peptides, as
demonstrated herein. Moreover, the definition of HLA motifs and
supermotifs also allows one to engineer highly cross-reactive
epitopes by identifying residues within a native peptide sequence
which can be analoged to confer upon the peptide certain
characteristics, e.g. greater cross-reactivity within the group of
HLA molecules that comprise a supertype, and/or greater binding
affinity for some or all of those HLA molecules. Examples of
analoging peptides to exhibit modulated binding affinity are set
forth in this example.
[0571] Analoging at Primary Anchor Residues
[0572] Peptide engineering strategies are implemented to further
increase the cross-reactivity of the epitopes. For example, the
main anchors of A2-supermotif-bearing peptides are altered, for
example, to introduce a preferred L, I, V, or M at position 2, and
I or V at the C-terminus.
[0573] To analyze the cross-reactivity of the analog peptides, each
engineered analog is initially tested for binding to the prototype
A2 supertype allele A*0201, then, if A*0201 binding capacity is
maintained, for A2-supertype cross-reactivity.
[0574] Alternatively, a peptide is confirmed as binding one or all
supertype members and then analoged to modulate binding affinity to
any one (or more) of the supertype members to add population
coverage.
[0575] The selection of analogs for immunogenicity in a cellular
screening analysis is typically further restricted by the capacity
of the parent wild type (WT) peptide to bind at least weakly, i.e.,
bind at an IC.sub.50 of 5000 nM or less, to three of more A2
supertype alleles. The rationale for this requirement is that the
WT peptides must be present endogenously in sufficient quantity to
be biologically relevant. Analoged peptides have been shown to have
increased immunogenicity and cross-reactivity by T cells specific
for the parent epitope (see, e.g., Parkhurst et al., J. Immunol.
157:2539, 1996; and Pogue et al., Proc. Natl. Acad. Sci. USA
92:8166, 1995).
[0576] In the cellular screening of these peptide analogs, it is
important to confirm that analog-specific CTLs are also able to
recognize the wild-type peptide and, when possible, target cells
that endogenously express the epitope.
[0577] Analoging of HLA-A3 and B7-Supermotif-Bearing Peptides
[0578] Analogs of HLA-A3 supermotif-bearing epitopes are generated
using strategies similar to those employed in analoging HLA-A2
supermotif-bearing peptides. For example, peptides binding to 3/5
of the A3-supertype molecules are engineered at primary anchor
residues to possess a preferred residue (V, S, M, or A) at position
2.
[0579] The analog peptides are then tested for the ability to bind
A*03 and A*11 (prototype A3 supertype alleles). Those peptides that
demonstrate .ltoreq.500 nM binding capacity are then confirmed as
having A3-supertype cross-reactivity.
[0580] Similarly to the A2- and A3-motif bearing peptides, peptides
binding 3 or more B7-supertype alleles can be improved, where
possible, to achieve increased cross-reactive binding or greater
binding affinity or binding half life. B7 supermotif-bearing
peptides are, for example, engineered to possess a preferred
residue (V, I, L, or F) at the C-terminal primary anchor position,
as demonstrated by Sidney et al. (J. Immunol. 157:3480-3490,
1996).
[0581] Analoging at primary anchor residues of other motif and/or
supermotif-bearing epitopes is performed in a like manner.
[0582] The analog peptides are then be confirmed for
immunogenicity, typically in a cellular screening assay. Again, it
is generally important to demonstrate that analog-specific CTLs are
also able to recognize the wild-type peptide and, when possible,
targets that endogenously express the epitope.
[0583] Analoging at Secondary Anchor Residues
[0584] Moreover, HLA supermotifs are of value in engineering highly
cross-reactive peptides and/or peptides that bind HLA molecules
with increased affinity by identifying particular residues at
secondary anchor positions that are associated with such
properties. For example, the binding capacity of a B7
supermotif-bearing peptide with an F residue at position 1 is
analyzed. The peptide is then analoged to, for example, substitute
L for F at position 1. The analoged peptide is evaluated for
increased binding affinity, binding half life and/or increased
cross-reactivity. Such a procedure identifies analoged peptides
with enhanced properties.
[0585] Engineered analogs with sufficiently improved binding
capacity or cross-reactivity can also be tested for immunogenicity
in HLA-B7-transgenic mice, following for example, IFA immunization
or lipopeptide immunization. Analoged peptides are additionally
tested for the ability to stimulate a recall response using PBMC
from patients with 151P3D4-expressing tumors.
[0586] Other Analoging Strategies
[0587] Another form of peptide analoging, unrelated to anchor
positions, involves the substitution of a cysteine with
.alpha.-amino butyric acid. Due to its chemical nature, cysteine
has the propensity to form disulfide bridges and sufficiently alter
the peptide structurally so as to reduce binding capacity.
Substitution of .alpha.-amino butyric acid for cysteine not only
alleviates this problem, but has been shown to improve binding and
crossbinding capabilities in some instances (see, e.g., the review
by Sette et al., In: Persistent Viral Infections, Eds. R. Ahmed and
I. Chen, John Wiley & Sons, England, 1999).
[0588] Thus, by the use of single amino acid substitutions, the
binding properties and/or cross-reactivity of peptide ligands for
HLA supertype molecules can be modulated.
Example 16
[0589] Identification and Confirmation of 151P3D4-derived Sequences
with HLA-DR Binding Motifs
[0590] Peptide epitopes bearing an HLA class II supermotif or motif
are identified and confirmed as outlined below using methodology
similar to that described for HLA Class I peptides.
[0591] Selection of HLA-DR-Supermotif-Bearing Epitopes.
[0592] To identify 151P3D4-derived, HLA class II HTL epitopes, a
151P3D4 antigen is analyzed for the presence of sequences bearing
an HLA-DR-motif or supermotif. Specifically, 15-mer sequences are
selected comprising a DR-supermotif, comprising a 9-mer core, and
three-residue N- and C-terminal flanking regions (15 amino acids
total).
[0593] Protocols for predicting peptide binding to DR molecules
have been developed (Southwood et al., J. Immunol. 160:3363-3373,
1998). These protocols, specific for individual DR molecules, allow
the scoring, and ranking, of 9-mer core regions. Each protocol not
only scores peptide sequences for the presence of DR-supermotif
primary anchors (i.e., at position 1 and position 6) within a 9-mer
core, but additionally evaluates sequences for the presence of
secondary anchors. Using allele-specific selection tables (see,
e.g., Southwood et al., ibid.), it has been found that these
protocols efficiently select peptide sequences with a high
probability of binding a particular DR molecule. Additionally, it
has been found that performing these protocols in tandem,
specifically those for DR1, DR4w4, and DR7, can efficiently select
DR cross-reactive peptides.
[0594] The 151P3D4-derived peptides identified above are tested for
their binding capacity for various common HLA-DR molecules. All
peptides are initially tested for binding to the DR molecules in
the primary panel: DR1, DR4w4, and DR7. Peptides binding at least
two of these three DR molecules are then tested for binding to
DR2w2 .beta.1, DR2w2 .beta.2, DR6w19, and DR9 molecules in
secondary assays. Finally, peptides binding at least two of the
four secondary panel DR molecules, and thus cumulatively at least
four of seven different DR molecules, are screened for binding to
DR4w15, DR5w11, and DR8w2 molecules in tertiary assays. Peptides
binding at least seven of the ten DR molecules comprising the
primary, secondary, and tertiary screening assays are considered
cross-reactive DR binders. 151P3D4-derived peptides found to bind
common HLA-DR alleles are of particular interest.
[0595] Selection of DR3 Motif Peptides
[0596] Because HLA-DR3 is an allele that is prevalent in Caucasian,
Black, and Hispanic populations, DR3 binding capacity is a relevant
criterion in the selection of HTL epitopes. Thus, peptides shown to
be candidates may also be assayed for their DR3 binding capacity.
However, in view of the binding specificity of the DR3 motif,
peptides binding only to DR3 can also be considered as candidates
for inclusion in a vaccine formulation.
[0597] To efficiently identify peptides that bind DR3, target
151P3D4 antigens are analyzed for sequences carrying one of the two
DR3-specific binding motifs reported by Geluk et al. (J. Immunol.
152:5742-5748, 1994). The corresponding peptides are then
synthesized and confirmed as having the ability to bind DR3 with an
affinity of 1 .mu.M or better, i.e., less than 1 .mu.M. Peptides
are found that meet this binding criterion and qualify as HLA class
II high affinity binders.
[0598] DR3 binding epitopes identified in this manner are included
in vaccine compositions with DR supermotif-bearing peptide
epitopes.
[0599] Similarly to the case of HLA class I motif-bearing peptides,
the class II motif-bearing peptides are analoged to improve
affinity or cross-reactivity. For example, aspartic acid at
position 4 of the 9-mer core sequence is an optimal residue for DR3
binding, and substitution for that residue often improves DR 3
binding.
Example 17
[0600] Immunogenicity of 151P3D4-Derived HTL Epitopes
[0601] This example determines immunogenic DR supermotif- and DR3
motif-bearing epitopes among those identified using the methodology
set forth herein.
[0602] Immunogenicity of HTL epitopes are confirmed in a manner
analogous to the determination of immunogenicity of CTL epitopes,
by assessing the ability to stimulate HTL responses and/or by using
appropriate transgenic mouse models. Immunogenicity is determined
by screening for: 1.) in vitro primary induction using normal PBMC
or 2.) recall responses from patients who have 151P3D4-expressing
tumors.
Example 18
[0603] Calculation of Phenotypic Frequencies of HLA-Supertypes in
Various Ethnic Backgrounds to Determine Breadth of Population
Coverage
[0604] This example illustrates the assessment of the breadth of
population coverage of a vaccine composition comprised of multiple
epitopes comprising multiple supermotifs and/or motifs.
[0605] In order to analyze population coverage, gene frequencies of
HLA alleles are determined. Gene frequencies for each HLA allele
are calculated from antigen or allele frequencies utilizing the
binomial distribution formulae gf=1-(SQRT(1-af)) (see, e.g., Sidney
et al., Human Immunol. 45:79-93, 1996). To obtain overall
phenotypic frequencies, cumulative gene frequencies are calculated,
and the cumulative antigen frequencies derived by the use of the
inverse formula [af=1-(1-Cgf).sup.2].
[0606] Where frequency data is not available at the level of DNA
typing, correspondence to the serologically defined antigen
frequencies is assumed. To obtain total potential supertype
population coverage no linkage disequilibrium is assumed, and only
alleles confirmed to belong to each of the supertypes are included
(minimal estimates). Estimates of total potential coverage achieved
by inter-loci combinations are made by adding to the A coverage the
proportion of the non-A covered population that could be expected
to be covered by the B alleles considered (e.g., total=A+B*(1-A)).
Confirmed members of the A3-like supertype are A3, A11, A31,
A*3301, and A*6801. Although the A3-like supertype may also include
A34, A66, and A*7401, these alleles were not included in overall
frequency calculations. Likewise, confirmed members of the A2-like
supertype family are A*0201, A*0202, A*0203, A*0204, A*0205,
A*0206, A*0207, A*6802, and A*6901. Finally, the B7-like
supertype-confirmed alleles are: B7, B*3501-03, B51, B*5301,
B*5401, B*5501-2, B*5601, B*6701, and B*7801 (potentially also
B*1401, B*3504-06, B*4201, and B*5602).
[0607] Population coverage achieved by combining the A2-, A3- and
B7-supertypes is approximately 86% in five major ethnic groups.
Coverage may be extended by including peptides bearing the A1 and
A24 motifs. On average, A1 is present in 12% and A24 in 29% of the
population across five different major ethnic groups (Caucasian,
North American Black, Chinese, Japanese, and Hispanic). Together,
these alleles are represented with an average frequency of 39% in
these same ethnic populations. The total coverage across the major
ethnicities when A1 and A24 are combined with the coverage of the
A2-, A3- and B7-supertype alleles is >95%. An analogous approach
can be used to estimate population coverage achieved with
combinations of class II motif-bearing epitopes.
[0608] Immunogenicity studies in humans (e.g., Bertoni et al., J.
Clin. Invest. 100:503, 1997; Doolan et al., Immunity 7:97, 1997;
and Threlkeld et al., J. Immunol. 159:1648, 1997) have shown that
highly cross-reactive binding peptides are almost always recognized
as epitopes. The use of highly cross-reactive binding peptides is
an important selection criterion in identifying candidate epitopes
for inclusion in a vaccine that is immunogenic in a diverse
population.
[0609] With a sufficient number of epitopes (as disclosed herein
and from the art), an average population coverage is predicted to
be greater than 95% in each of five major ethnic populations. The
game theory Monte Carlo simulation analysis, which is known in the
art (see e.g., Osborne, M. J. and Rubinstein, A. "A course in game
theory" MIT Press, 1994), can be used to estimate what percentage
of the individuals in a population comprised of the Caucasian,
North American Black, Japanese, Chinese, and Hispanic ethnic groups
would recognize the vaccine epitopes described herein. A preferred
percentage is 90%. A more preferred percentage is 95%.
Example 19
[0610] CTL Recognition of Endogenously Processed Antigens after
Priming
[0611] This example confirms that CTL induced by native or analoged
peptide epitopes identified and selected as described herein
recognize endogenously synthesized, i.e., native antigens.
[0612] Effector cells isolated from transgenic mice that are
immunized with peptide epitopes, for example HLA-A2
supermotif-bearing epitopes, are re-stimulated in vitro using
peptide-coated stimulator cells. Six days later, effector cells are
assayed for cytotoxicity and the cell lines that contain
peptide-specific cytotoxic activity are further re-stimulated. An
additional six days later, these cell lines are tested for
cytotoxic activity on .sup.51Cr labeled Jurkat-A2.1/K.sup.b target
cells in the absence or presence of peptide, and also tested on
.sup.51Cr labeled target cells bearing the endogenously synthesized
antigen, i.e. cells that are stably transfected with 151P3D4
expression vectors.
[0613] The results demonstrate that CTL lines obtained from animals
primed with peptide epitope recognize endogenously synthesized
151P3D4 antigen. The choice of transgenic mouse model to be used
for such an analysis depends upon the epitope(s) that are being
evaluated. In addition to HLA-A*0201/K.sup.b transgenic mice,
several other transgenic mouse models including mice with human
A11, which may also be used to evaluate A3 epitopes, and B7 alleles
have been characterized and others (e.g., transgenic mice for
HLA-A1 and A24) are being developed. HLA-DR1 and HLA-DR3 mouse
models have also been developed, which may be used to evaluate HTL
epitopes.
Example 20
[0614] Activity of CTL-HTL Conjugated Epitopes in Transgenic
Mice
[0615] This example illustrates the induction of CTLs and HTLs in
transgenic mice, by use of a 151P3D4-derived CTL and HTL peptide
vaccine compositions. The vaccine composition used herein comprise
peptides to be administered to a patient with a 151P3D4-expressing
tumor. The peptide composition can comprise multiple CTL and/or HTL
epitopes. The epitopes are identified using methodology as
described herein. This example also illustrates that enhanced
immunogenicity can be achieved by inclusion of one or more HTL
epitopes in a CTL vaccine composition; such a peptide composition
can comprise an HTL epitope conjugated to a CTL epitope. The CTL
epitope can be one that binds to multiple HLA family members at an
affinity of 500 nM or less, or analogs of that epitope. The
peptides may be lipidated, if desired.
[0616] Immunization procedures: Immunization of transgenic mice is
performed as described (Alexander et al., J. Immunol.
159:4753-4761, 1997). For example, A2/K.sup.b mice, which are
transgenic for the human HLA A2.1 allele and are used to confirm
the immunogenicity of HLA-A*0201 motif- or HLA-A2
supermotif-bearing epitopes, and are primed subcutaneously (base of
the tail) with a 0.1 ml of peptide in Incomplete Freund's Adjuvant,
or if the peptide composition is a lipidated CTL/HTL conjugate, in
DMSO/saline, or if the peptide composition is a polypeptide, in PBS
or Incomplete Freund's Adjuvant. Seven days after priming,
splenocytes obtained from these animals are restimulated with
syngenic irradiated LPS-activated lymphoblasts coated with
peptide.
[0617] Cell lines: Target cells for peptide-specific cytotoxicity
assays are Jurkat cells transfected with the HLA-A2.1/K.sup.b
chimeric gene (e.g., Vitiello et al., J. Exp. Med. 173:1007,
1991)
[0618] In vitro CTL activation: One week after priming, spleen
cells (30.times.10.sup.6 cells/flask) are co-cultured at 37.degree.
C. with syngeneic, irradiated (3000 rads), peptide coated
lymphoblasts (10.times.10.sup.6 cells/flask) in 10 ml of culture
medium/T25 flask. After six days, effector cells are harvested and
assayed for cytotoxic activity.
[0619] Assay for cytotoxic activity: Target cells (1.0 to
1.5.times.10.sup.6) are incubated at 37.degree. C. in the presence
of 200 .mu.l of .sup.51Cr. After 60 minutes, cells are washed three
times and resuspended in R10 medium. Peptide is added where
required at a concentration of 1 .mu.g/ml. For the assay, 10.sup.4
51Cr-labeled target cells are added to different concentrations of
effector cells (final volume of 200 .mu.l) in U-bottom 96-well
plates. After a six hour incubation period at 37.degree. C., a 0.1
ml aliquot of supernatant is removed from each well and
radioactivity is determined in a Micromedic automatic gamma
counter. The percent specific lysis is determined by the formula:
percent specific release=100.times.(experimental
release-spontaneous release)/(maximum release-spontaneous release).
To facilitate comparison between separate CTL assays run under the
same conditions, % .sup.51Cr release data is expressed as lytic
units/10.sup.6 cells. One lytic unit is arbitrarily defined as the
number of effector cells required to achieve 30% lysis of 10,000
target cells in a six hour .sup.51Cr release assay. To obtain
specific lytic units/10.sup.6, the lytic units/10.sup.6 obtained in
the absence of peptide is subtracted from the lytic units/10.sup.6
obtained in the presence of peptide. For example, if 30% .sup.51Cr
release is obtained at the effector (E): target (T) ratio of 50:1
(i.e., 5.times.10.sup.5 effector cells for 10,000 targets) in the
absence of peptide and 5:1 (i.e., 5.times.10.sup.4 effector cells
for 10,000 targets) in the presence of peptide, the specific lytic
units would be: [(1/50,000)-(1/500,000)].times.10.sup.6=18 LU.
[0620] The results are analyzed to assess the magnitude of the CTL
responses of animals injected with the immunogenic CTL/HTL
conjugate vaccine preparation and are compared to the magnitude of
the CTL response achieved using, for example, CTL epitopes as
outlined above in the Example entitled "Confirmation of
Immunogenicity." Analyses similar to this may be performed to
confirm the immunogenicity of peptide conjugates containing
multiple CTL epitopes and/or multiple HTL epitopes. In accordance
with these procedures, it is found that a CTL response is induced,
and concomitantly that an HTL response is induced upon
administration of such compositions.
Example 21
[0621] Selection of CTL and HTL Epitopes for Inclusion in a
151P3D4-Specific Vaccine.
[0622] This example illustrates a procedure for selecting peptide
epitopes for vaccine compositions of the invention. The peptides in
the composition can be in the form of a nucleic acid sequence,
either single or one or more sequences (i.e., minigene) that
encodes peptide(s), or can be single and/or polyepitopic
peptides.
[0623] The following principles are utilized when selecting a
plurality of epitopes for inclusion in a vaccine composition. Each
of the following principles is balanced in order to make the
selection.
[0624] Epitopes are selected which, upon administration, mimic
immune responses that are correlated with 151P3D4 clearance. The
number of epitopes used depends on observations of patients who
spontaneously clear 151P3D4. For example, if it has been observed
that patients who spontaneously clear 151P3D4-expressing cells
generate an immune response to at least three (3) epitopes from
151P3D4 antigen, then at least three epitopes should be included
for HLA class I. A similar rationale is used to determine HLA class
II epitopes.
[0625] Epitopes are often selected that have a binding affinity of
an IC.sub.50 of 500 nM or less for an HLA class I molecule, or for
class II, an IC.sub.50 of 1000 nM or less; or HLA Class I peptides
with high binding scores from the BIMAS web site, at URL
bimas.dcrt.nih.gov/.
[0626] In order to achieve broad coverage of the vaccine through
out a diverse population, sufficient supermotif bearing peptides,
or a sufficient array of allele-specific motif bearing peptides,
are selected to give broad population coverage. In one embodiment,
epitopes are selected to provide at least 80% population coverage.
A Monte Carlo analysis, a statistical evaluation known in the art,
can be employed to assess breadth, or redundancy, of population
coverage.
[0627] When creating polyepitopic compositions, or a minigene that
encodes same, it is typically desirable to generate the smallest
peptide possible that encompasses the epitopes of interest. The
principles employed are similar, if not the same, as those employed
when selecting a peptide comprising nested epitopes. For example, a
protein sequence for the vaccine composition is selected because it
has maximal number of epitopes contained within the sequence, i.e.,
it has a high concentration of epitopes. Epitopes may be nested or
overlapping (i.e., frame shifted relative to one another). For
example, with overlapping epitopes, two 9-mer epitopes and one
10-mer epitope can be present in a 10 amino acid peptide. Each
epitope can be exposed and bound by an HLA molecule upon
administration of such a peptide. A multi-epitopic, peptide can be
generated synthetically, recombinantly, or via cleavage from the
native source. Alternatively, an analog can be made of this native
sequence, whereby one or more of the epitopes comprise
substitutions that alter the cross-reactivity and/or binding
affinity properties of the polyepitopic peptide. Such a vaccine
composition is administered for therapeutic or prophylactic
purposes. This embodiment provides for the possibility that an as
yet undiscovered aspect of immune system processing will apply to
the native nested sequence and thereby facilitate the production of
therapeutic or prophylactic immune response-inducing vaccine
compositions. Additionally such an embodiment provides for the
possibility of motif-bearing epitopes for an HLA makeup that is
presently unknown. Furthermore, this embodiment (absent the
creating of any analogs) directs the immune response to multiple
peptide sequences that are actually present in 151P3D4, thus
avoiding the need to evaluate any junctional epitopes. Lastly, the
embodiment provides an economy of scale when producing nucleic acid
vaccine compositions. Related to this embodiment, computer programs
can be derived in accordance with principles in the art, which
identify in a target sequence, the greatest number of epitopes per
sequence length.
[0628] A vaccine composition comprised of selected peptides, when
administered, is safe, efficacious, and elicits an immune response
similar in magnitude to an immune response that controls or clears
cells that bear or overexpress 151P3D4.
Example 22
[0629] Construction of "Minigene" Multi-Enitope DNA Plasmids
[0630] This example discusses the construction of a minigene
expression plasmid. Minigene plasmids may, of course, contain
various configurations of B cell, CTL and/or HTL epitopes or
epitope analogs as described herein.
[0631] A minigene expression plasmid typically includes multiple
CTL and HTL peptide epitopes. In the present example, HLA-A2, -A3,
-B7 supermotif-bearing peptide epitopes and HLA-A1 and -A24
motif-bearing peptide epitopes are used in conjunction with DR
supermotif-bearing epitopes and/or DR3 epitopes. HLA class I
supermotif or motif-bearing peptide epitopes derived 151P3D4, are
selected such that multiple supermotifs/motifs are represented to
ensure broad population coverage. Similarly, HLA class II epitopes
are selected from 151P3D4 to provide broad population coverage,
i.e. both HLA DR-1-4-7 supermotif-bearing epitopes and HLA DR-3
motif-bearing epitopes are selected for inclusion in the minigene
construct. The selected CTL and HTL epitopes are then incorporated
into a minigene for expression in an expression vector.
[0632] Such a construct may additionally include sequences that
direct the HTL epitopes to the endoplasmic reticulum. For example,
the Ii protein may be fused to one or more HTL epitopes as
described in the art, wherein the CLIP sequence of the Ii protein
is removed and replaced with an HLA class II epitope sequence so
that HLA class II epitope is directed to the endoplasmic reticulum,
where the epitope binds to an HLA class II molecules.
[0633] This example illustrates the methods to be used for
construction of a minigene-bearing expression plasmid. Other
expression vectors that may be used for ninigene compositions are
available and known to those of skill in the art.
[0634] The minigene DNA plasmid of this example contains a
consensus Kozak sequence and a consensus murine kappa Ig-light
chain signal sequence followed by CTL and/or HTL epitopes selected
in accordance with principles disclosed herein. The sequence
encodes an open reading frame fused to the Myc and His antibody
epitope tag coded for by the pcDNA 3.1 Myc-His vector.
[0635] Overlapping oligonucleotides that can, for example, average
about 70 nucleotides in length with 15 nucleotide overlaps, are
synthesized and HPLC-purified. The oligonucleotides encode the
selected peptide epitopes as well as appropriate linker
nucleotides, Kozak sequence, and signal sequence. The final
multiepitope minigene is assembled by extending the overlapping
oligonucleotides in three sets of reactions using PCR. A
Perkin/Elmer 9600 PCR machine is used and a total of 30 cycles are
performed using the following conditions: 95.degree. C. for 15 sec,
annealing temperature (5.degree. below the lowest calculated Tm of
each primer pair) for 30 sec, and 72.degree. C. for 1 min.
[0636] For example, a minigene is prepared as follows. For a first
PCR reaction, 5 .mu.g of each of two oligonucleotides are annealed
and extended: In an example using eight oligonucleotides, i.e.,
four pairs of primers, oligonucleotides 1+2, 3+4, 5+6, and 7+8 are
combined in 100 .mu.l reactions contain Pfu polymerase buffer
(1.times.=10 mM KCL, 10 mM (NH4).sub.2SO.sub.4, 20 mM
Tris-chloride, pH 8.75, 2 mM MgSO.sub.4, 0.1% Triton X-100, 100
.mu.g/ml BSA), 0.25 mM each dNTP, and 2.5 U of Pfu polymerase. The
full-length dimer products are gel-purified, and two reactions
containing the product of 1+2 and 3+4, and the product of 5+6 and
7+8 are mixed, annealed, and extended for 10 cycles. Half of the
two reactions are then mixed, and cycles of annealing and extension
carried out before flanking primers are added to amplify the full
length product. The full-length product is gel-purified and cloned
into pCR-blunt (Invitrogen) and individual clones are screened by
sequencing.
Example 23
[0637] The Plasmid Construct and the Degree to Which It Induces
Immunogenicity.
[0638] The degree to which a plasmid construct, for example a
plasmid constructed in accordance with the previous Example, is
able to induce immunogenicity is confirmed in vitro by determining
epitope presentation by APC following transduction or transfection
of the APC with an epitope-expressing nucleic acid construct. Such
a study determines "antigenicity" and allows the use of human APC.
The assay determines the ability of the epitope to be presented by
the APC in a context that is recognized by a T cell by quantifying
the density of epitope-HLA class I complexes on the cell surface.
Quantitation can be performed by directly measuring the amount of
peptide eluted from the APC (see, e.g., Sijts et al., J. Immunol.
156:683-692, 1996; Demotz et al., Nature 342:682-684, 1989); or the
number of peptide-HLA class I complexes can be estimated by
measuring the amount of lysis or lymphokine release induced by
diseased or transfected target cells, and then determining the
concentration of peptide necessary to obtain equivalent levels of
lysis or lymphokine release (see, e.g., Kageyama et al., J.
Immunol. 154:567-576, 1995).
[0639] Alternatively, immunogenicity is confirmed through in vivo
injections into mice and subsequent in vitro assessment of CTL and
HTL activity, which are analyzed using cytotoxicity and
proliferation assays, respectively, as detailed e.g., in Alexander
et al., Immunity 1:751-761, 1994.
[0640] For example, to confirm the capacity of a DNA minigene
construct containing at least one HLA-A2 supermotif peptide to
induce CTLs in vivo, HLA-A2.1/K.sup.b transgenic mice, for example,
are immunized intramuscularly with 100 .mu.g of naked cDNA. As a
means of comparing the level of CTLs induced by cDNA immunization,
a control group of animals is also immunized with an actual peptide
composition that comprises multiple epitopes synthesized as a
single polypeptide as they would be encoded by the minigene.
[0641] Splenocytes from immunized animals are stimulated twice with
each of the respective compositions (peptide epitopes encoded in
the minigene or the polyepitopic peptide), then assayed for
peptide-specific cytotoxic activity in a .sup.51Cr release assay.
The results indicate the magnitude of the CTL response directed
against the A2-restricted epitope, thus indicating the in vivo
immunogenicity of the minigene vaccine and polyepitopic
vaccine.
[0642] It is, therefore, found that the minigene elicits immune
responses directed toward the HLA-A2 supermotif peptide epitopes as
does the polyepitopic peptide vaccine. A similar analysis is also
performed using other HLA-A3 and HLA-B7 transgenic mouse models to
assess CTL induction by HLA-A3 and HLA-B7 motif or supermotif
epitopes, whereby it is also found that the minigene elicits
appropriate immune responses directed toward the provided
epitopes.
[0643] To confirm the capacity of a class II epitope-encoding
minigene to induce HTLs in vivo, DR transgenic mice, or for those
epitopes that cross react with the appropriate mouse MHC molecule,
I-A.sup.b-restricted mice, for example, are immunized
intramuscularly with 100 .mu.g of plasmid DNA. As a means of
comparing the level of HTLs induced by DNA immunization, a group of
control animals is also immunized with an actual peptide
composition emulsified in complete Freund's adjuvant. CD4+ T cells,
i.e. HTLs, are purified from splenocytes of immunized animals and
stimulated with each of the respective compositions (peptides
encoded in the minigene). The HTL response is measured using a
.sup.3H-thymidine incorporation proliferation assay, (see, e.g.,
Alexander et al. Immunity 1:751-761, 1994). The results indicate
the magnitude of the HTL response, thus demonstrating the in vivo
immunogenicity of the minigene.
[0644] DNA minigenes, constructed as described in the previous
Example, can also be confirmed as a vaccine in combination with a
boosting agent using a prime boost protocol. The boosting agent can
consist of recombinant protein (e.g., Barnett et al., Aids Res. and
Human Retroviruses 14, Supplement 3:S299-S309, 1998) or recombinant
vaccinia, for example, expressing a minigene or DNA encoding the
complete protein of interest (see, e.g., Hanke et al., Vaccine
16:439-445, 1998; Sedegah et al., Proc. Natl. Acad. Sci USA
95:7648-53, 1998; Hanke and McMichael, Immunol. Letters 66:177-181,
1999; and Robinson et al., Nature Med. 5:526-34, 1999).
[0645] For example, the efficacy of the DNA minigene used in a
prime boost protocol is initially evaluated in transgenic mice. In
this example, A2.1/K.sup.b transgenic mice are immunized IM with
100 .mu.g of a DNA minigene encoding the immunogenic peptides
including at least one HLA-A2 supermotif-bearing peptide. After an
incubation period (ranging from 3-9 weeks), the mice are boosted IP
with 10.sup.7 pfu/mouse of a recombinant vaccinia virus expressing
the same sequence encoded by the DNA minigene. Control mice are
immunized with 100 .mu.g of DNA or recombinant vaccinia without the
minigene sequence, or with DNA encoding the minigene, but without
the vaccinia boost. After an additional incubation period of two
weeks, splenocytes from the mice are immediately assayed for
peptide-specific activity in an ELISPOT assay. Additionally,
splenocytes are stimulated in vitro with the A2-restricted peptide
epitopes encoded in the minigene and recombinant vaccinia, then
assayed for peptide-specific activity in an alpha, beta and/or
gamma IFN ELISA.
[0646] It is found that the minigene utilized in a prime-boost
protocol elicits greater immune responses toward the HLA-A2
supermotif peptides than with DNA alone. Such an analysis can also
be performed using HLA-A11 or HLA-B7 transgenic mouse models to
assess CTL induction by HLA-A3 or HLA-B7 motif or supermotif
epitopes. The use of prime boost protocols in humans is described
below in the Example entitled "Induction of CTL Responses Using a
Prime Boost Protocol."
Example 24
[0647] Peptide Compositions for Prophylactic Uses
[0648] Vaccine compositions of the present invention can be used to
prevent 151P3D4 expression in persons who are at risk for tumors
that bear this antigen. For example, a polyepitopic peptide epitope
composition (or a nucleic acid comprising the same) containing
multiple CTL and HTL epitopes such as those selected in the above
Examples, which are also selected to target greater than 80% of the
population, is administered to individuals at risk for a
151P3D4-associated tumor.
[0649] For example, a peptide-based composition is provided as a
single polypeptide that encompasses multiple epitopes. The vaccine
is typically administered in a physiological solution that
comprises an adjuvant, such as Incomplete Freunds Adjuvant. The
dose of peptide for the initial immunization is from about 1 to
about 50,000 .mu.g, generally 100-5,000 .mu.g, for a 70 kg patient.
The initial administration of vaccine is followed by booster
dosages at 4 weeks followed by evaluation of the magnitude of the
immune response in the patient, by techniques that determine the
presence of epitope-specific CTL populations in a PBMC sample.
Additional booster doses are administered as required. The
composition is found to be both safe and efficacious as a
prophylaxis against 151P3D4-associated disease.
[0650] Alternatively, a composition typically comprising
transfecting agents is used for the administration of a nucleic
acid-based vaccine in accordance with methodologies known in the
art and disclosed herein.
Example 25
[0651] Polyepitopic Vaccine Compositions Derived from Native
151P3D4 Sequences
[0652] A native 151P3D4 polyprotein sequence is analyzed,
preferably using computer algorithms defined for each class I
and/or class II supermotif or motif, to identify "relatively short"
regions of the polyprotein that comprise multiple epitopes. The
"relatively short" regions are preferably less in length than an
entire native antigen. This relatively short sequence that contains
multiple distinct or overlapping, "nested" epitopes can be used to
generate a minigene construct. The construct is engineered to
express the peptide, which corresponds to the native protein
sequence. The "relatively short" peptide is generally less than 250
amino acids in length, often less than 100 amino acids in length,
preferably less than 75 amino acids in length, and more preferably
less than 50 amino acids in length. The protein sequence of the
vaccine composition is selected because it has maximal number of
epitopes contained within the sequence, i.e., it has a high
concentration of epitopes. As noted herein, epitope motifs may be
nested or overlapping (i.e., frame shifted relative to one
another). For example, with overlapping epitopes, two 9-mer
epitopes and one 10-mer epitope can be present in a 10 amino acid
peptide. Such a vaccine composition is administered for therapeutic
or prophylactic purposes.
[0653] The vaccine composition will include, for example, multiple
CTL epitopes from 151P3D4 antigen and at least one HTL epitope.
This polyepitopic native sequence is administered either as a
peptide or as a nucleic acid sequence which encodes the peptide.
Alternatively, an analog can be made of this native sequence,
whereby one or more of the epitopes comprise substitutions that
alter the cross-reactivity and/or binding affinity properties of
the polyepitopic peptide.
[0654] The embodiment of this example provides for the possibility
that an as yet undiscovered aspect of immune system processing will
apply to the native nested sequence and thereby facilitate the
production of therapeutic or prophylactic immune response-inducing
vaccine compositions. Additionally, such an embodiment provides for
the possibility of motif-bearing epitopes for an HLA makeup(s) that
is presently unknown. Furthermore, this embodiment (excluding an
analoged embodiment) directs the immune response to multiple
peptide sequences that are actually present in native 151P3D4, thus
avoiding the need to evaluate any junctional epitopes. Lastly, the
embodiment provides an economy of scale when producing peptide or
nucleic acid vaccine compositions.
[0655] Related to this embodiment, computer programs are available
in the art which can be used to identify in a target sequence, the
greatest number of epitopes per sequence length.
Example 26
[0656] Polyepitopic Vaccine Compositions from Multiple Antigens
[0657] The 151P3D4 peptide epitopes of the present invention are
used in conjunction with epitopes from other target
tumor-associated antigens, to create a vaccine composition that is
useful for the prevention or treatment of cancer that expresses
151P3D4 and such other antigens. For example, a vaccine composition
can be provided as a single polypeptide that incorporates multiple
epitopes from 151P3D4 as well as tumor-associated antigens that are
often expressed with a target cancer associated with 151P3D4
expression, or can be administered as a composition comprising a
cocktail of one or more discrete epitopes. Alternatively, the
vaccine can be administered as a minigene construct or as dendritic
cells which have been loaded with the peptide epitopes in
vitro.
Example 27
[0658] Use of Peptides to Evaluate an Immune Response
[0659] Peptides of the invention may be used to analyze an immune
response for the presence of specific antibodies, CTL or HTL
directed to 151P3D4. Such an analysis can be performed in a manner
described by Ogg et al., Science 279:2103-2106, 1998. In this
Example, peptides in accordance with the invention are used as a
reagent for diagnostic or prognostic purposes, not as an
immunogen.
[0660] In this example highly sensitive human leukocyte antigen
tetrameric complexes ("tetramers") are used for a cross-sectional
analysis of, for example, 151P3D4 HLA-A*0201-specific CTL
frequencies from HLA A*0201-positive individuals at different
stages of disease or following immunization comprising a 151P3D4
peptide containing an A*0201 motif Tetrameric complexes are
synthesized as described (Musey et al., N. Engl. J. Med. 337:1267,
1997). Briefly, purified HLA heavy chain (A*0201 in this example)
and .beta.2-microglobulin are synthesized by means of a prokaryotic
expression system. The heavy chain is modified by deletion of the
transmembrane-cytosolic tail and COOH-terminal addition of a
sequence containing a BirA enzymatic biotinylation site. The heavy
chain, .beta.2-microglobulin, and peptide are refolded by dilution.
The 45-kD refolded product is isolated by fast protein liquid
chromatography and then biotinylated by BirA in the presence of
biotin (Sigma, St. Louis, Mo.), adenosine 5' triphosphate and
magnesium. Streptavidin-phycoerythrin conjugate is added in a 1:4
molar ratio, and the tetrameric product is concentrated to 1 mg/ml.
The resulting product is referred to as tetramer-phycoerythrin.
[0661] For the analysis of patient blood samples, approximately one
million PBMCs are centrifuged at 300 g for 5 minutes and
resuspended in 50 .mu.l of cold phosphate-buffered saline.
Tri-color analysis is performed with the tetramer-phycoerythrin,
along with anti-CD8-Tricolor, and anti-CD38. The PBMCs are
incubated with tetramer and antibodies on ice for 30 to 60 min and
then washed twice before formaldehyde fixation. Gates are applied
to contain >99.98% of control samples. Controls for the
tetramers include both A*0201-negative individuals and
A*0201-positive non-diseased donors. The percentage of cells
stained with the tetramer is then determined by flow cytometry. The
results indicate the number of cells in the PBMC sample that
contain epitope-restricted CTLs, thereby readily indicating the
extent of immune response to the 151P3D4 epitope, and thus the
status of exposure to 151P3D4, or exposure to a vaccine that
elicits a protective or therapeutic response.
Example 28
[0662] Use of Peptide Epitopes to Evaluate Recall Responses
[0663] The peptide epitopes of the invention are used as reagents
to evaluate T cell responses, such as acute or recall responses, in
patients. Such an analysis may be performed on patients who have
recovered from 151P3D4-associated disease or who have been
vaccinated with a 151P3D4 vaccine.
[0664] For example, the class I restricted CTL response of persons
who have been vaccinated may be analyzed. The vaccine may be any
151P3D4 vaccine. PBMC are collected from vaccinated individuals and
HLA typed. Appropriate peptide epitopes of the invention that,
optimally, bear supermotifs to provide cross-reactivity with
multiple HLA supertype family members, are then used for analysis
of samples derived from individuals who bear that HLA type.
[0665] PBMC from vaccinated individuals are separated on
Ficoll-Histopaque density gradients (Sigma Chemical Co., St. Louis,
Mo.), washed three times in HBSS (GIBCO Laboratories), resuspended
in RPMI-1640 (GIBCO Laboratories) supplemented with L-glutamine (2
mM), penicillin (50 U/ml), streptomycin (50 .mu.g/ml), and Hepes
(10 mM) containing 10% heat-inactivated human AB serum (complete
RPMI) and plated using microculture formats. A synthetic peptide
comprising an epitope of the invention is added at 10 .mu.g/ml to
each well and HBV core 128-140 epitope is added at 1 .mu.g/ml to
each well as a source of T cell help during the first week of
stimulation.
[0666] In the microculture format, 4.times.10.sup.5 PBMC are
stimulated with peptide in 8 replicate cultures in 96-well round
bottom plate in 100 .mu.l/well of complete RPMI. On days 3 and 10,
100 .mu.l of complete RPMI and 20 U/ml final concentration of rIL-2
are added to each well. On day 7 the cultures are transferred into
a 96-well flat-bottom plate and restimulated with peptide, rIL-2
and 10.sup.5 irradiated (3,000 rad) autologous feeder cells. The
cultures are tested for cytotoxic activity on day 14. A positive
CTL response requires two or more of the eight replicate cultures
to display greater than 10% specific .sup.51Cr release, based on
comparison with non-diseased control subjects as previously
described (Rehermann, et al., Nature Med. 2:1104,1108, 1996;
Rehermann et al., J. Clin. Invest. 97:1655-1665, 1996; and
Rehermann et al. J. Clin. Invest. 98:1432-1440, 1996).
[0667] Target cell lines are autologous and allogeneic
EBV-transformed B-LCL that are either purchased from the American
Society for Histocompatibility and Immunogenetics (ASHI, Boston,
Mass.) or established from the pool of patients as described
(Guilhot, et al. J. Virol. 66:2670-2678, 1992).
[0668] Cytotoxicity assays are performed in the following manner.
Target cells consist of either allogeneic HLA-matched or autologous
EBV-transformed B lymphoblastoid cell line that are incubated
overnight with the synthetic peptide epitope of the invention at 10
.mu.M, and labeled with 100 .mu.Ci of .sup.51Cr (Amersham Corp.,
Arlington Heights, Ill.) for 1 hour after which they are washed
four times with HBSS.
[0669] Cytolytic activity is determined in a standard 4-h, split
well .sup.51Cr release assay using U-bottomed 96 well plates
containing 3,000 targets/well. Stimulated PBMC are tested at
effector/target (E/T) ratios of 20-50:1 on day 14. Percent
cytotoxicity is determined from the formula:
100.times.[(experimental release-spontaneous release)/maximum
release-spontaneous release)]. Maximum release is determined by
lysis of targets by detergent (2% Triton X-100; Sigma Chemical Co.,
St. Louis, Mo.). Spontaneous release is <25% of maximum release
for all experiments.
[0670] The results of such an analysis indicate the extent to which
HLA-restricted CTL populations have been stimulated by previous
exposure to 151P3D4 or a 151P3D4 vaccine.
[0671] Similarly, Class II restricted HTL responses may also be
analyzed. Purified PBMC are cultured in a 96-well flat bottom plate
at a density of 1.5.times.10.sup.5 cells/well and are stimulated
with 10 .mu.g/ml synthetic peptide of the invention, whole 151P3D4
antigen, or PHA. Cells are routinely plated in replicates of 4-6
wells for each condition. After seven days of culture, the medium
is removed and replaced with fresh medium containing 10 U/ml IL-2.
Two days later, 1 .mu.Ci .sup.3H-thymidine is added to each well
and incubation is continued for an additional 18 hours. Cellular
DNA is then harvested on glass fiber mats and analyzed for
.sup.3H-thymidine incorporation. Antigen-specific T cell
proliferation is calculated as the ratio of .sup.3H-thymidine
incorporation in the presence of antigen divided by the
.sup.3H-thymidine incorporation in the absence of antigen.
Example 29
[0672] Induction of Specific CTL Response in Humans
[0673] A human clinical trial for an immunogenic composition
comprising CTL and HTL epitopes of the invention is set up as an
IND Phase I, dose escalation study and carried out as a randomized,
double-blind, placebo-controlled trial. Such a trial is designed,
for example, as follows:
[0674] A total of about 27 individuals are enrolled and divided
into 3 groups:
[0675] Group I: 3 subjects are injected with placebo and 6 subjects
are injected with 5 .mu.g of peptide composition;
[0676] Group II: 3 subjects are injected with placebo and 6
subjects are injected with 50 .mu.g peptide composition;
[0677] Group III: 3 subjects are injected with placebo and 6
subjects are injected with 500 .mu.g of peptide composition.
[0678] After 4 weeks following the first injection, all subjects
receive a booster inoculation at the same dosage.
[0679] The endpoints measured in this study relate to the safety
and tolerability of the peptide composition as well as its
immunogenicity. Cellular immune responses to the peptide
composition are an index of the intrinsic activity of this the
peptide composition, and can therefore be viewed as a measure of
biological efficacy. The following summarize the clinical and
laboratory data that relate to safety and efficacy endpoints.
[0680] Safety: The incidence of adverse events is monitored in the
placebo and drug treatment group and assessed in terms of degree
and reversibility.
[0681] Evaluation of Vaccine Efficacy: For evaluation of vaccine
efficacy, subjects are bled before and after injection. Peripheral
blood mononuclear cells are isolated from fresh heparinized blood
by Ficoll-Hypaque density gradient centrifugation, aliquoted in
freezing media and stored frozen. Samples are assayed for CTL and
HTL activity.
[0682] The vaccine is found to be both safe and efficacious.
Example 30
[0683] Phase II Trials in Patients Expressing 151P3D4
[0684] Phase II trials are performed to study the effect of
administering the CTL-HTL peptide compositions to patients having
cancer that expresses 151P3D4. The main objectives of the trial are
to determine an effective dose and regimen for inducing CTLs in
cancer patients that express 151P3D4, to establish the safety of
inducing a CTL and HTL response in these patients, and to see to
what extent activation of CTLs improves the clinical picture of
these patients, as manifested, e.g., by the reduction and/or
shrinking of lesions. Such a study is designed, for example, as
follows:
[0685] The studies are performed in multiple centers. The trial
design is an open-label, uncontrolled, dose escalation protocol
wherein the peptide composition is administered as a single dose
followed six weeks later by a single booster shot of the same dose.
The dosages are 50, 500 and 5,000 micrograms per injection.
Drug-associated adverse effects (severity and reversibility) are
recorded.
[0686] There are three patient groupings. The first group is
injected with 50 micrograms of the peptide composition and the
second and third groups with 500 and 5,000 micrograms of peptide
composition, respectively. The patients within each group range in
age from 21-65 and represent diverse ethnic backgrounds. All of
them have a tumor that expresses 151P3D4.
[0687] Clinical manifestations or antigen-specific T-cell responses
are monitored to assess the effects of administering the peptide
compositions. The vaccine composition is found to be both safe and
efficacious in the treatment of 151P3D4-associated disease.
Example 31
[0688] Induction of CTL Responses Using a Prime Boost Protocol
[0689] A prime boost protocol similar in its underlying principle
to that used to confirm the efficacy of a DNA vaccine in transgenic
mice, such as described above in the Example entitled "The Plasmid
Construct and the Degree to Which It Induces Immunogenicity," can
also be used for the administration of the vaccine to humans. Such
a vaccine regimen can include an initial administration of, for
example, naked DNA followed by a boost using recombinant virus
encoding the vaccine, or recombinant protein/polypeptide or a
peptide mixture administered in an adjuvant.
[0690] For example, the initial immunization may be performed using
an expression vector, such as that constructed in the Example
entitled "Construction of "Minigene" Multi-Epitope DNA Plasmids" in
the form of naked nucleic acid administered IM (or SC or ID) in the
amounts of 0.5-5 mg at multiple sites. The nucleic acid (0.1 to
1000 .mu.g) can also be administered using a gene gun. Following an
incubation period of 3-4 weeks, a booster dose is then
administered. The booster can be recombinant fowlpox virus
administered at a dose of 5-10.sup.7 to 5.times.10.sup.9 pfu. An
alternative recombinant virus, such as an MVA, canarypox,
adenovirus, or adeno-associated virus, can also be used for the
booster, or the polyepitopic protein or a mixture of the peptides
can be administered. For evaluation of vaccine efficacy, patient
blood samples are obtained before immunization as well as at
intervals following administration of the initial vaccine and
booster doses of the vaccine. Peripheral blood mononuclear cells
are isolated from fresh heparinized blood by Ficoll-Hypaque density
gradient centrifugation, aliquoted in freezing media and stored
frozen. Samples are assayed for CTL and HTL activity.
[0691] Analysis of the results indicates that a magnitude of
response sufficient to achieve a therapeutic or protective immunity
against 151P3D4 is generated.
Example 32
[0692] Administration of Vaccine Compositions Using Dendritic Cells
(DC)
[0693] Vaccines comprising peptide epitopes of the invention can be
administered using APCs, or "professional" APCs such as DC. In this
example, peptide-pulsed DC are administered to a patient to
stimulate a CTL response in vivo. In this method, dendritic cells
are isolated, expanded, and pulsed with a vaccine comprising
peptide CTL and HTL epitopes of the invention. The dendritic cells
are infused back into the patient to elicit CTL and HTL responses
in vivo. The induced CTL and HTL then destroy or facilitate
destruction, respectively, of the target cells that bear the
151P3D4 protein from which the epitopes in the vaccine are
derived.
[0694] For example, a cocktail of epitope-comprising peptides is
administered ex vivo to PBMC, or isolated DC therefrom. A
pharmaceutical to facilitate harvesting of DC can be used, such as
Progenipoietin.TM. (Monsanto, St. Louis, Mo.) or GM-CSF/IL-4. After
pulsing the DC with peptides, and prior to reinfusion into
patients, the DC are washed to remove unbound peptides.
[0695] As appreciated clinically, and readily determined by one of
skill based on clinical outcomes, the number of DC reinfused into
the patient can vary (see, e.g., Nature Med. 4:328, 1998; Nature
Med. 2:52, 1996 and Prostate 32:272, 1997). Although
2-50.times.10.sup.6 DC per patient are typically administered,
larger number of DC, such as 10.sup.7 or 10.sup.8 can also be
provided. Such cell populations typically contain between 50-90%
DC.
[0696] In some embodiments, peptide-loaded PBMC are injected into
patients without purification of the DC. For example, PBMC
generated after treatment with an agent such as Progenipoietin.TM.
are injected into patients without purification of the DC. The
total number of PBMC that are administered often ranges from
10.sup.8 to 10.sup.10. Generally, the cell doses injected into
patients is based on the percentage of DC in the blood of each
patient, as determined, for example, by immunofluorescence analysis
with specific anti-DC antibodies. Thus, for example, if
Progenipoietin.TM. mobilizes 2% DC in the peripheral blood of a
given patient, and that patient is to receive 5.times.10.sup.6 DC,
then the patient will be injected with a total of
2.5.times.10.sup.8 peptide-loaded PBMC. The percent DC mobilized by
an agent such as Progenipoietin.TM. is typically estimated to be
between 2-10%, but can vary as appreciated by one of skill in the
art.
[0697] Ex vivo activation of CTL/HTL responses
[0698] Alternatively, ex vivo CTL or HTL responses to 151P3D4
antigens can be induced by incubating, in tissue culture, the
patient's, or genetically compatible, CTL or HTL precursor cells
together with a source of APC, such as DC, and immunogenic
peptides. After an appropriate incubation time (typically about
7-28 days), in which the precursor cells are activated and expanded
into effector cells, the cells are infused into the patient, where
they will destroy (CTL) or facilitate destruction (HTL) of their
specific target cells, i.e., tumor cells.
Example 33
[0699] An Alternative Method of Identifying and Confirming
Motif-Bearing Peptides
[0700] Another method of identifying and confirming motif-bearing
peptides is to elute them from cells bearing defined MHC molecules.
For example, EBV transformed B cell lines used for tissue typing
have been extensively characterized to determine which HLA
molecules they express. In certain cases these cells express only a
single type of HLA molecule. These cells can be transfected with
nucleic acids that express the antigen of interest, e.g. 151P3D4.
Peptides produced by endogenous antigen processing of peptides
produced as a result of transfection will then bind to HLA
molecules within the cell and be transported and displayed on the
cell's surface. Peptides are then eluted from the HLA molecules by
exposure to mild acid conditions and their amino acid sequence
determined, e.g., by mass spectral analysis (e.g., Kubo et al., J.
Immunol. 152:3913, 1994). Because the majority of peptides that
bind a particular HLA molecule are motif-bearing, this is an
alternative modality for obtaining the motif-bearing peptides
correlated with the particular HLA molecule expressed on the
cell.
[0701] Alternatively, cell lines that do not express endogenous HLA
molecules can be transfected with an expression construct encoding
a single HLA allele. These cells can then be used as described,
i.e., they can then be transfected with nucleic acids that encode
151P3D4 to isolate peptides corresponding to 151P3D4 that have been
presented on the cell surface. Peptides obtained from such an
analysis will bear motif(s) that correspond to binding to the
single HLA allele that is expressed in the cell.
[0702] As appreciated by one in the art, one can perform a similar
analysis on a cell bearing more than one HLA allele and
subsequently determine peptides specific for each HLA allele
expressed. Moreover, one of skill would also recognize that means
other than transfection, such as loading with a protein antigen,
can be used to provide a source of antigen to the cell.
Example 34
[0703] Complementary Polynucleotides
[0704] Sequences complementary to the 151P3D4-encoding sequences,
or any parts thereof, are used to detect, decrease, or inhibit
expression of naturally occurring 151P3D4. Although use of
oligonucleotides comprising from about 15 to 30 base pairs is
described, essentially the same procedure is used with smaller or
with larger sequence fragments. Appropriate oligonucleotides are
designed using, e.g., OLIGO 4.06 software (National Biosciences)
and the coding sequence of 151P3D4. To inhibit transcription, a
complementary oligonucleotide is designed from the most unique 5'
sequence and used to prevent promoter binding to the coding
sequence. To inhibit translation, a complementary oligonucleotide
is designed to prevent ribosomal binding to a 151P3D4-encoding
transcript.
Example 35
[0705] Purification of Naturally-Occurring or Recombinant 151P3D4
Using 151P3D4-Specific Antibodies
[0706] Naturally occurring or recombinant 151P3D4 is substantially
purified by immunoaffinity chromatography using antibodies specific
for 151P3D4. An immunoaffinity column is constructed by covalently
coupling anti-151P3D4 antibody to an activated chromatographic
resin, such as CNBr-activated SEPHAROSE (Amersham Pharmacia
Biotech). After the coupling, the resin is blocked and washed
according to the manufacturer's instructions.
[0707] Media containing 151P3D4 are passed over the immunoaffinity
column, and the column is washed under conditions that allow the
preferential absorbance of 151P3D4 (e.g., high ionic strength
buffers in the presence of detergent). The column is eluted under
conditions that disrupt antibody/151P3D4 binding (e.g., a buffer of
pH 2 to pH 3, or a high concentration of a chaotrope, such as urea
or thiocyanate ion), and GCR.P is collected.
Example 36
[0708] Identification of Molecules Which Interact with 151P3D4
[0709] 151P3D4, or biologically active fragments thereof, are
labeled with 121 1 Bolton-Hunter reagent. (See, e.g., Bolton et al.
(1973) Biochem. J. 133:529.) Candidate molecules previously arrayed
in the wells of a multi-well plate are incubated with the labeled
151P3D4, washed, and any wells with labeled 151P3D4 complex are
assayed. Data obtained using different concentrations of 151P3D4
are used to calculate values for the number, affinity, and
association of 151P3D4 with the candidate molecules.
Example 37
[0710] In vivo Assay for 151P3D4 Tumor Growth Promotion
[0711] The effect of the 151P3D4 protein on tumor cell growth is
evaluated in vivo by evaluating tumor development and growth of
cells expressing or lacking 151P3D4. For example, SCID mice are
injected subcutaneously on each flank with 1.times.10.sup.6 of
either 3T3, bladder, kidney or ovary cancer cell lines (e.g.
SCABER, J82, PA-1, CaOv3, A498 or 769P cells) containing tkNeo
empty vector or 151P3D4. At least two strategies may be used: (1)
Constitutive 151P3D4 expression under regulation of a promoter such
as a constitutive promoter obtained from the genomes of viruses
such as polyoma virus, fowlpox virus (UK 2,211,504 published Jul.
5, 1989), adenovirus (such as Adenovirus 2), bovine papilloma
virus, avian sarcoma virus, cytomegalovirus, a retrovirus,
hepatitis-B virus and Simian Virus 40 (SV40), or from heterologous
mammalian promoters, e.g., the actin promoter or an immunoglobulin
promoter, provided such promoters are compatible with the host cell
systems, and (2) Regulated expression under control of an inducible
vector system, such as ecdysone, tetracycline, etc., provided such
promoters are compatible with the host cell systems. Tumor volume
is then monitored by caliper measurement at the appearance of
palpable tumors and followed over time to determine if
151P3D4-expressing cells grow at a faster rate and whether tumors
produced by 151P3D4-expressing cells demonstrate characteristics of
altered aggressiveness (e.g. enhanced metastasis, vascularization,
reduced responsiveness to chemotherapeutic drugs).
[0712] Additionally, mice can be implanted with 1.times.10.sup.5 of
the same cells orthotopically to determine if 151P3D4 has an effect
on local growth in the bladder, kidney or ovary, and whether
151P3D4 affects the ability of the cells to metastasize,
specifically to lymph nodes, adrenal, liver and bone (Miki T et al,
Oncol Res. 2001;12:209; Fu X et al, Int J Cancer. 1991, 49:938;
Kiguchi Ket al, Clin Exp Metastasis. 1998, 16:751).
[0713] The assay is also useful to determine the 151P3D4 inhibitory
effect of candidate therapeutic compositions, such as for example,
151P3D4 intrabodies, 151P3D4 antisense molecules and ribozymes.
Example 38
[0714] 151P3D4 Monoclonal Antibody-Mediated Inhibition of Bladder,
Kidney and Ovarian Tumors In Vivo
[0715] The significant expression of 151P3D4 in cancer tissues,
together with its restrictive expression in normal tissues makes
151P3D4 a good target for antibody therapy. Similarly, 151P3D4 is a
target for T cell-based immunotherapy. Thus, the therapeutic
efficacy of anti-151P3D4 mAbs in human bladder cancer xenograft
mouse models is evaluated by using recombinant cell lines such as
SCABER-151P3D4, J82-151P3D4, and 3T3-151P3D4 (see, e.g., Kaighn, M.
E., et al., Invest Urol, 1979. 17(1): p. 16-23). Similarly
anti-151P3D4 mAbs are evaluated in human kidney and ovarian cancer
xenograft models using recombinant cell lines such as A498-151P3D4
and PA1-151P3D4.
[0716] Antibody efficacy on tumor growth and metastasis formation
is studied, e.g., in a mouse orthotopic bladder cancer xenograft
model, a mouse kidney cancer xenograft model and a mouse ovarian
cancer xenograft model. The antibodies can be unconjugated, as
discussed in this Example, or can be conjugated to a therapeutic
modality, as appreciated in the art. Anti-151P3D4 mAbs inhibit
formation of kidney, ovarian and bladder xenografts. Anti-151P3D4
mAbs also retard the growth of established orthotopic tumors and
prolonged survival of tumor-bearing nice. These results indicate
the utility of anti-151P3D4 mAbs in the treatment of local and
advanced stages of ovarian, kidney and bladder cancer. (See, e.g.,
Saffran, D., et al., PNAS 10:1073-1078 or
www.pnas.org/cgi/doi/10.1- 073/pnas.051624698).
[0717] Administration of the anti-151P3D4 mAbs led to retardation
of established orthotopic tumor growth and inhibition of metastasis
to distant sites, resulting in a significant prolongation in the
survival of tumor-bearing mice. These studies indicate that 151P3D4
as an attractive target for immunotherapy and demonstrate the
therapeutic potential of anti-151P3D4 mAbs for the treatment of
local and metastatic cancer. This example demonstrates that
unconjugated 151P3D4 monoclonal antibodies are effective to inhibit
the growth of human bladder, kidney and ovarian tumor xenografts
grown in SCID mice; accordingly a combination of such efficacious
monoclonal antibodies is also effective.
[0718] Tumor Inhibition Using Multiple Unconjugated 151P3D4
mAbs
[0719] Materials and Methods
[0720] 151P3D4 Monoclonal Antibodies:
[0721] Monoclonal antibodies are raised against 151P3D4 as
described in the Example entitled "Generation of 151P3D4 Monoclonal
Antibodies (mAbs)." The antibodies are characterized by ELISA,
Western blot, FACS, and immunoprecipitation for their capacity to
bind 151P3D4. Epitope mapping data for the anti-151P3D4 mAbs, as
determined by ELISA and Western analysis, recognize epitopes on the
151P3D4 protein. Immunohistochemical analysis of prostate cancer
tissues and cells with these antibodies is performed.
[0722] The monoclonal antibodies are purified from ascites or
hybridoma tissue culture supernatants by Protein-G Sepharose
chromatography, dialyzed against PBS, filter sterilized, and stored
at -20.degree. C. Protein determinations are performed by a
Bradford assay (Bio-Rad, Hercules, Calif.). A therapeutic
monoclonal antibody or a cocktail comprising a mixture of
individual monoclonal antibodies is prepared and used for the
treatment of mice receiving subcutaneous or orthotopic injections
of SCABER, J82, A498, 769P, CaOv1 or PA1 tumor xenografts.
[0723] Cell Lines
[0724] The bladder, kidney and ovary carcinoma cell lines, SCABER,
J82, A498, 769P, CaOv1 and PA1 as well as the fibroblast line NIH
3T3 (American Type Culture Collection) are maintained in DMEM
supplemented with L-glutamine and 10% FBS.
[0725] A SCABER-151P3D4, J82-151P3D4, A498-151P3D4, 769P-151P3D4,
CaOv1-151P3D4, PA1-151P3D4 and 3T3-151P3D4 cell populations are
generated by retroviral gene transfer as described in Hubert, R.
S., et al., Proc Natl Acad Sci USA, 1999. 96(25): 14523.
[0726] Xenograft Mouse Models.
[0727] Subcutaneous (s.c.) tumors are generated by injection of
1.times.10.sup.6 cancer cells mixed at a 1:1 dilution with Matrigel
(Collaborative Research) in the right flank of male SCID mice. To
test antibody efficacy on tumor formation, i.p. antibody injections
are started on the same day as tumor-cell injections. As a control,
mice are injected with either purified mouse IgG (ICN) or PBS; or a
purified monoclonal antibody that recognizes an irrelevant antigen
not expressed in human cells. Tumor sizes are determined by caliper
measurements, and the tumor volume is calculated as:
Length.times.Width.times.Height. Mice with s.c. tumors greater than
1.5 cm in diameter are sacrificed.
[0728] Orthotopic injections are performed under anesthesia by
using ketamine/xylazine. For bladder orthotopic studies, an
incision is made through the abdomen to expose the bladder, and
tumor cells (5.times.10.sup.5) mixed with Matrigel are injected
into the bladder wall in a 10-.mu.l volume. To monitor tumor
growth, mice are palpated and blood is collected on a weekly basis
to measure BTA levels. For kidney and ovary orthopotic models, an
incision is made through the abdominal muscles to expose the kidney
or the ovary. Tumor cells mixed with Matrigel are injected under
the kidney capsule or into the ovary in a 10-.mu.l volume (Yoshida
Y et al, Anticancer Res. 1998, 18:327; Ahn et al, Tumour Biol.
2001, 22:146). To monitor tumor growth, blood is collected on a
weekly basis measuring G250 and SM047 levels. The mice are
segregated into groups for the appropriate treatments, with
anti-151P3D4 or control mAbs being injected i.p.
[0729] Anti-151P3D4 mAbs Inhibit Growth of 151P3D4-Expressing
Xenograft-Cancer Tumors
[0730] The effect of anti-151P3D4 mAbs on tumor formation is tested
on the growth and progression of bladder, kidney and ovarian cancer
xenografts using UC3-151P3D4, J82-151P3D4, A498-151P3D4,
769P-151P3D4, CaOv1-151P3D4 and PA1-151P3D4 orthotopic models. As
compared with the s.c. tumor model, the orthotopic model, which
requires injection of tumor cells directly in the mouse bladder,
kidney and ovary, respectively, results in a local tumor growth,
development of metastasis in distal sites, deterioration of mouse
health, and subsequent death (Saffran, D., et al., PNAS supra; Fu,
X., et al., Int J Cancer, 1992. 52(6): p. 987-90; Kubota, T., J
Cell Biochem, 1994. 56(1): p. 4-8). The features make the
orthotopic model more representative of human disease progression
and allowed us to follow the therapeutic effect of mAbs on
clinically relevant end points.
[0731] Accordingly, tumor cells are injected into the mouse
bladder, kidney or ovary, and 2 days later, the mice are segregated
into two groups and treated with either: a) 200-500 .mu.g, of
anti-151P3D4 Ab, or b) PBS three times per week for two to five
weeks.
[0732] A major advantage of the orthotopic cancer models is the
ability to study the development of metastases. Formation of
metastasis in mice bearing established orthotopic tumors is studies
by IHC analysis on lung sections using an antibody against a
tumor-specific cell-surface protein such as anti-CK20 for bladder
cancer, anti-G250 for kidney cancer and SM047 antibody for ovarian
cancer models (Lin S et al, Cancer Detect Prev. 2001;25:202;
McCluggage W et al, Histopathol 2001, 38:542).
[0733] Mice bearing established orthotopic tumors are administered
1000 .mu.g injections of either anti-151P3D4 mAb or PBS over a
4-week period. Mice in both groups are allowed to establish a high
tumor burden, to ensure a high frequency of metastasis formation in
mouse lungs. Mice then are killed and their bladders, livers, bone
and lungs are analyzed for the presence of tumor cells by IHC
analysis.
[0734] These studies demonstrate a broad anti-tumor efficacy of
anti-151P3D4 antibodies on initiation and progression of prostate
and kidney cancer in xenograft mouse models. Anti-151P3D4
antibodies inhibit tumor formation of tumors as well as retarding
the growth of already established tumors and prolong the survival
of treated mice. Moreover, anti-151P3D4 mAbs demonstrate a dramatic
inhibitory effect on the spread of local bladder, kidney and
ovarian tumor to distal sites, even in the presence of a large
tumor burden. Thus, anti-151P3D4 mAbs are efficacious on major
clinically relevant end points (tumor growth), prolongation of
survival, and health.
Example 39
[0735] Therapeutic and Diagnostic Use of Anti-151P3D4 Antibodies in
Humans.
[0736] Anti-151P3D4 monoclonal antibodies are safely and
effectively used for diagnostic, prophylactic, prognostic and/or
therapeutic purposes in humans. Western blot and
immunohistochemical analysis of cancer tissues and cancer
xenografts with anti-151P3D4 mAb show strong extensive staining in
carcinoma but significantly lower or undetectable levels in normal
tissues. Detection of 151P3D4 in carcinoma and in metastatic
disease demonstrates the usefulness of the mAb as a diagnostic
and/or prognostic indicator. Anti-151P3D4 antibodies are therefore
used in diagnostic applications such as immunohistochemistry of
kidney biopsy specimens to detect cancer from suspect patients.
[0737] As determined by flow cytometry, anti-151P3D4 mAb
specifically binds to carcinoma cells. Thus, anti-151P3D4
antibodies are used in diagnostic whole body imaging applications,
such as radioimmunoscintigraphy and radioimmunotherapy, (see, e.g.,
Potamianos S., et. al. Anticancer Res 20(2A):925-948 (2000)) for
the detection of localized and metastatic cancers that exhibit
expression of 151P3D4. Shedding or release of an extracellular
domain of 151P3D4 into the extracellular milieu, such as that seen
for alkaline phosphodiesterase B10 (Meerson, N. R., Hepatology
27:563-568 (1998)), allows diagnostic detection of 151P3D4 by
anti-151P3D4 antibodies in serum and/or urine samples from suspect
patients.
[0738] Anti-151P3D4 antibodies that specifically bind 151P3D4 are
used in therapeutic applications for the treatment of cancers that
express 151P3D4. Anti-151P3D4 antibodies are used as an
unconjugated modality and as conjugated form in which the
antibodies are attached to one of various therapeutic or imaging
modalities well known in the art, such as a prodrugs, enzymes or
radioisotopes. In preclinical studies, unconjugated and conjugated
anti-151P3D4 antibodies are tested for efficacy of tumor prevention
and growth inhibition in the SCID mouse cancer xenograft models,
e.g., kidney cancer models AGS-K3 and AGS-K6, (see, e.g., the
Example entitled "151P3D4 Monoclonal Antibody-mediated Inhibition
of Bladder and Lung Tumors In Vivo"). Conjugated and unconjugated
anti-151P3D4 antibodies are used as a therapeutic modality in human
clinical trials either alone or in combination with other
treatments as described in following Examples.
Example 40
[0739] Human Clinical Trials for the Treatment and Diagnosis of
Human Carcinomas Through Use of Human Anti-151P3D4 Antibodies In
Vivo
[0740] Antibodies are used in accordance with the present invention
which recognize an epitope on 151P3D4, and are used in the
treatment of certain tumors such as those listed in Table I. Based
upon a number of factors, including 151P3D4 expression levels,
tumors such as those listed in Table I are presently preferred
indications. In connection with each of these indications, three
clinical approaches are successfully pursued.
[0741] I.) Adjunctive therapy: In adjunctive therapy, patients are
treated with anti-151P3D4 antibodies in combination with a
chemotherapeutic or antineoplastic agent and/or radiation therapy.
Primary cancer targets, such as those listed in Table I, are
treated under standard protocols by the addition anti-151P3D4
antibodies to standard first and second line therapy. Protocol
designs address effectiveness as assessed by reduction in tumor
mass as well as the ability to reduce usual doses of standard
chemotherapy. These dosage reductions allow additional and/or
prolonged therapy by reducing dose-related toxicity of the
chemotherapeutic agent. Anti-151P3D4 antibodies are utilized in
several adjunctive clinical trials in combination with the
chemotherapeutic or antineoplastic agents adriamycin (advanced
prostrate carcinoma), cisplatin (advanced head and neck and lung
carcinomas), taxol (breast cancer), and doxorubicin
(preclinical).
[0742] II.) Monotherapy: In connection with the use of the
anti-151P3D4 antibodies in monotherapy of tumors, the antibodies
are administered to patients without a chemotherapeutic or
antineoplastic agent. In one embodiment, monotherapy is conducted
clinically in end stage cancer patients with extensive metastatic
disease. Patients show some disease stabilization. Trials
demonstrate an effect in refractory patients with cancerous
tumors.
[0743] III.) Imaging Agent: Through binding a radionuclide (e.g.,
iodine or yttrium (I.sup.131, Y.sup.90) to anti-151P3D4 antibodies,
the radiolabeled antibodies are utilized as a diagnostic and/or
imaging agent. In such a role, the labeled antibodies localize to
both solid tumors, as well as, metastatic lesions of cells
expressing 151P3D4. In connection with the use of the anti-151P3D4
antibodies as imaging agents, the antibodies are used as an adjunct
to surgical treatment of solid tumors, as both a pre-surgical
screen as well as a post-operative follow-up to determine what
tumor remains and/or returns. In one embodiment, a (.sup.111
In)-151P3D4 antibody is used as an imaging agent in a Phase I human
clinical trial in patients having a carcinoma that expresses
151P3D4 (by analogy see, e.g., Divgi et al. J. Natl. Cancer Inst.
83:97-104 (1991)). Patients are followed with standard anterior and
posterior gamma camera. The results indicate that primary lesions
and metastatic lesions are identified
[0744] Dose and Route of Administration
[0745] As appreciated by those of ordinary skill in the art, dosing
considerations can be determined through comparison with the
analogous products that are in the clinic. Thus, anti-151P3D4
antibodies can be administered with doses in the range of 5 to 400
mg/m.sup.2, with the lower doses used, e.g., in connection with
safety studies. The affinity of anti-151P3D4 antibodies relative to
the affinity of a known antibody for its target is one parameter
used by those of skill in the art for determining analogous dose
regimens. Further, anti-151P3D4 antibodies that are fully human
antibodies, as compared to the chimeric antibody, have slower
clearance; accordingly, dosing in patients with such fully human
anti-151P3D4 antibodies can be lower, perhaps in the range of 50 to
300 mg/m.sup.2, and still remain efficacious. Dosing in mg/m.sup.2,
as opposed to the conventional measurement of dose in mg/kg, is a
measurement based on surface area and is a convenient dosing
measurement that is designed to include patients of all sizes from
infants to adults.
[0746] Three distinct delivery approaches are useful for delivery
of anti-151P3D4 antibodies. Conventional intravenous delivery is
one standard delivery technique for many tumors. However, in
connection with tumors in the peritoneal cavity, such as tumors of
the ovaries, biliary duct, other ducts, and the like,
intraperitoneal administration may prove favorable for obtaining
high dose of antibody at the tumor and to also minimize antibody
clearance. In a similar manner, certain solid tumors possess
vasculature that is appropriate for regional perfusion. Regional
perfusion allows for a high dose of antibody at the site of a tumor
and minimizes short term clearance of the antibody.
[0747] Clinical Development Plan (CDP)
[0748] Overview: The CDP follows and develops treatments of
anti-151P3D4 antibodies in connection with adjunctive therapy,
monotherapy, and as an imaging agent. Trials initially demonstrate
safety and thereafter confirm efficacy in repeat doses. Trails are
open label comparing standard chemotherapy with standard therapy
plus anti-151P3D4 antibodies. As will be appreciated, one criteria
that can be utilized in connection with enrollment of patients is
151P3D4 expression levels in their tumors as determined by
biopsy.
[0749] As with any protein or antibody infusion-based therapeutic,
safety concerns are related primarily to (i) cytokine release
syndrome, i.e., hypotension, fever, shaking, chills; (ii) the
development of an immunogenic response to the material (i.e.,
development of human antibodies by the patient to the antibody
therapeutic, or HAHA response); and, (iii) toxicity to normal cells
that express 151P3D4. Standard tests and follow-up are utilized to
monitor each of these safety concerns. Anti-151P3D4 antibodies are
found to be safe upon human administration.
Example 41
[0750] Human Clinical Trial Adjunctive Therapy with Human
Anti-151P3D4 Antibody and Chemotherapeutic Agent
[0751] A phase I human clinical trial is initiated to assess the
safety of six intravenous doses of a human anti-151P3D4 antibody in
connection with the treatment of a solid tumor, e.g., a cancer of a
tissue listed in Table I. In the study, the safety of single doses
of anti-151P3D4 antibodies when utilized as an adjunctive therapy
to an antineoplastic or chemotherapeutic agent, such as cisplatin,
topotecan, doxorubicin, adriamycin, taxol, or the like, is
assessed. The trial design includes delivery of six single doses of
an anti-151P3D4 antibody with dosage of antibody escalating from
approximately about 25 mg/m.sup.2 to about 275 mg/m.sup.2 over the
course of the treatment in accordance with the following
schedule:
3 Day 0 Day 7 Day 14 Day 21 Day 28 Day 35 mAb Dose 25 mg/m.sup.2 75
mg/m.sup.2 125 mg/m.sup.2 175 mg/m.sup.2 225 mg/m.sup.2 275
mg/m.sup.2 Chemotherapy + + + + + + (standard dose)
[0752] Patients are closely followed for one-week following each
administration of antibody and chemotherapy. In particular,
patients are assessed for the safety concerns mentioned above: (i)
cytokine release syndrome, i.e., hypotension, fever, shaking,
chills; (ii) the development of an immunogenic response to the
material (i.e., development of human antibodies by the patient to
the human antibody therapeutic, or HAHA response); and, (iii)
toxicity to normal cells that express 151P3D4. Standard tests and
follow-up are utilized to monitor each of these safety concerns.
Patients are also assessed for clinical outcome, and particularly
reduction in tumor mass as evidenced by MRI or other imaging.
[0753] The anti-151P3D4 antibodies are demonstrated to be safe and
efficacious, Phase II trials confirm the efficacy and refine
optimum dosing.
Example 42
[0754] Human Clinical Trial: Monotherapy with Human Anti-151P3D4
Antibody
[0755] Anti-151P3D4 antibodies are safe in connection with the
above-discussed adjunctive trial, a Phase II human clinical trial
confirms the efficacy and optimum dosing for monotherapy. Such
trial is accomplished, and entails the same safety and outcome
analyses, to the above-described adjunctive trial with the
exception being that patients do not receive chemotherapy
concurrently with the receipt of doses of anti-151P3D4
antibodies.
Example 43
[0756] Human Clinical Trial: Diagnostic Imaging with Anti-151P3D4
Antibody
[0757] Once again, as the adjunctive therapy discussed above is
safe within the safety criteria discussed above, a human clinical
trial is conducted concerning the use of anti-151P3D4 antibodies as
a diagnostic imaging agent. The protocol is designed in a
substantially similar manner to those described in the art, such as
in Divgi et al. J. Natl. Cancer Inst. 83:97-104 (1991). The
antibodies are found to be both safe and efficacious when used as a
diagnostic modality.
Example 44
[0758] Homology Comparison of 151P3D4 to Known Sequences
[0759] Two variants of 151P3D4 have been identified, 151P3D4 v.1
and v 2. The 151P3D4 v.1 gene exhibits strong homology to a
previously cloned gene, namely the human cartilage linking protein
1 (gi 4503053), and shows 100% identity to that gene over the
entire length of the protein (FIG. 4B). In addition, the 151P3D4
v.1 protein shows homology to the bovine and rat homologs of the
human cartilage linking protein (gi 1709660 and gi 9506519) (FIGS.
4F and 4G). 151P3D4 v.1 is a 354 aa protein which localizes
primarily to the extracellular compartment (see Table XXI). The
second variant, 151P3D4 v.2, is a 721 aa protein, that shares
identity with 151P3D4 v.1 over 200 amino acids (Table LV and FIG.
4D). The 151P3D4 v.2 gene also exhibits homology to the human
cartilage link protein-1 (gi 4503053), showing 99% identity and 99%
homology to that protein (FIG. 4H). However, this homology between
variant 2 and cartilage link protein does not extend over the
entire length of variant 2, but is limited to the last 400 aa of
that protein. The first 400 aa of 151P3D4 v.2 show homology to
human ribosomal protein L13a of the 60S subunit (gi. 18574549) (see
Table XXI). Besides the addition of 400 aa at its N-terminus,
151P3D4 v.2 also differs from variant 1 in its localization
profile. 151P3D4 v.2 localizes to the cytosol, with potential
localization to the nucleus (see Table XXI). Motif analysis
revealed the presence of link motif as well as immunoglobulin
domain in both 151P3D4 variants (see Table XXI).
[0760] Cartilage link protein-1, a protein with a known link motif,
has been shown to regulate tissue remodeling, bone resorption and
protein interaction (Chen Q et al. Dev Biol. 1995, 172:293). The
importance of cartilage link protein 1 is illustrated in engineered
mice lacking cartilage link protein (Watanabe H, Yamada Y. Nat
Genet. 1999, 21:225). These mutant mice demonstrate defects in
cartilage and bone development. The cartilage link protein, via its
link motif, mediates cell adhesion of fibroblasts and other cells
to extracellular matrix (Yang B et al, Matrix Biol. 1998, 16:541).
The link motif is a binding domain for hyaluronic acid (Kohda D et
al, Cell. 1996, 86:767), with a structure very similar to type
C-lectin. It plays a role in the assembly of extracellular matrix,
cell adhesion, and migration (Kohda D et al, Cell. 1996, 86:767).
The immunoglobulin domain is a 100 aa long motif which includes a
conserved intra-domain disulfide bond. Immunoglobulin-like domains
participate in protein interactions (Wang J, Springer T A. Immunol
Rev. 1998, 163:197).
[0761] The presence of an immunoglobulin motif and a link motif
indicate that 151P3D4 regulates protein interactions and
participates in the process of cell adhesion, cell migration, tumor
formation and progression. By way of its protein interaction
domain, 151P3D4 functions in regulating signal transduction in
mammalian cells, thereby regulating gene expression and cellular
outcomes, including cell proliferation, survival, invasion,
motility, etc, all of which have a direct effect on tumor growth
and progression.
[0762] Accordingly, when 151P3D4 functions as a regulator of
protein interactions, cell adhesion, tumor formation, invasion or
cell signaling, 151P3D4 is used for therapeutic, diagnostic,
prognostic and/or preventative purposes. In addition, when a
variant of 151P3D4 is expressed in cancerous tissues, such as those
listed in Table I, they are used for therapeutic, diagnostic,
prognostic and/or preventative purposes.
Example 45
[0763] Regulation of Transcription
[0764] The localization of 151P3D4 coupled to the presence of
protein interaction domains within its sequence, indicate that
151P3D4 modulates the transcriptional regulation of eukaryotic
genes. Regulation of gene expression is confirmed, e.g., by
studying gene expression in cells expressing or lacking 151P3D4.
For this purpose, two types of experiments are performed.
[0765] In the first set of experiments, RNA from parental and
151P3D4-expressing cells are extracted and hybridized to
commercially available gene arrays (Clontech) (Smid-Koopman E et
al. Br J Cancer. 2000. 83:246). Resting cells as well as cells
treated with FBS, androgen or growth factors are compared.
Differentially expressed genes are identified in accordance with
procedures known in the art. The differentially expressed genes are
then mapped to biological pathways (Chen K et al. Thyroid. 2001.
11:41.).
[0766] In the second set of experiments, specific transcriptional
pathway activation is evaluated using commercially available
(Stratagene) luciferase reporter constructs including: NFkB-luc,
SRE-luc, ELK1-luc, ARE-luc, p53-luc, and CRE-luc. These
transcriptional reporters contain consensus binding sites for known
transcription factors that lie downstream of well-characterized
signal transduction pathways, and represent a good tool to
ascertain pathway activation and screen for positive and negative
modulators of pathway activation.
[0767] Thus, 151P3D4 plays a role in gene regulation, and it is
used as a target for diagnostic, prognostic, preventative and/or
therapeutic purposes.
Example 46
[0768] Identification and Confirmation of Potential Signal
Transduction Pathways
[0769] Many mammalian proteins have been reported to interact with
signaling molecules and to participate in regulating signaling
pathways. (J Neurochem. 2001; 76:217-223). In particular, protein
interaction motifs have been instrumental in inducing kinase
activation, recruitment of proteins and complex formation (Samelson
L. Annu Rev Immunol. 2002;20:371). Based on the presence of a
protein interacton motif, 151P3D4 regulates signaling pathways
important for cell growth and invasion. In addition, the 151P3D4
protein contains several phosphorylation sites (see Table XX)
indicating an association with specific signaling cascades. Using
immunoprecipitation and Western blotting techniques, proteins are
identified that associate with 151P3D4 and mediate signaling
events. Several pathways known to play a role in cancer biology can
be regulated by 151P3D4, including phospholipid pathways such as
PI3K, AKT, etc, adhesion and migration pathways, including FAK,
Rho, Rac-1, .beta.-catenin, etc, as well as mitogenic/survival
cascades such as ERK, p38, etc (Cell Growth Differ. 2000,11:279; J
Biol Chem. 1999, 274:801; Oncogene. 2000, 19:3003, J. Cell Biol.
1997, 138:913.).
[0770] To confirm that 151P3D4 directly or indirectly activates
known signal transduction pathways in cells, luciferase (luc) based
transcriptional reporter assays are carried out in cells expressing
individual genes. These transcriptional reporters contain
consensus-binding sites for known transcription factors that lie
downstream of well-characterized signal transduction pathways. The
reporters and examples of these associated transcription factors,
signal transduction pathways, and activation stimuli are listed
below.
[0771] 1. NFkB-luc, NFkB/Re1; Ik-kinase/SAPK;
growth/apoptosis/stress
[0772] 2. SRE-luc, SRF/TCF/ELK1; MAPK/SAPK;
growth/differentiation
[0773] 3. AP-1-luc, FOS/JUN; MAPK/SAPK/PKC;
growth/apoptosis/stress
[0774] 4. ARE-luc, androgen receptor; steroids/MAPK;
growth/differentiation/apoptosis
[0775] 5. p53-luc, p53; SAPK; growth/differentiation/apoptosis
[0776] 6. CRE-luc, CREB/ATF2; PKA/p38; growth/apoptosis/stress
[0777] 7. TCF-luc, TCF/Lef; .beta.-catenin, Adhesion/invasion
[0778] Gene-mediated effects can be assayed in cells showing mRNA
expression. Luciferase reporter plasmids can be introduced by
lipid-mediated transfection (TFX-50, Promega). Luciferase activity,
an indicator of relative transcriptional activity, is measured by
incubation of cell extracts with luciferin substrate and
luminescence of the reaction is monitored in a luminometer.
[0779] Signaling pathways activated by 151P3D4 are mapped and used
for the identification and validation of therapeutic targets. When
151P3D4 is involved in cell signaling, it is used as target for
diagnostic, prognostic, preventative and/or therapeutic
purposes.
Example 47
[0780] Involvement in Tumor Progression
[0781] Based on the role of link motif in cell adhesion, cell
migration and tumor formation, the 151P3D4 gene can contribute to
tumor initiation and progression. The role of 151P3D4 in tumor
growth is confirmed in a variety of primary and transfected cell
lines including bladder, kidney and ovary cell lines, as well as
NIH 3T3 cells engineered to stably express 151P3D4. Parental cells
lacking 151P3D4 and cells expressing 151P3D4 are evaluated for cell
growth using a well-documented proliferation assay (Fraser S P,
Grimes J A, Djamgoz M B. Prostate. 2000;44:61, Johnson D E, Ochieng
J, Evans S L. Anticancer Drugs. 1996, 7:288).
[0782] To confirm the role of 151P3D4 in the transformation
process, its effect in colony forming assays is investigated.
Parental NIH-3T3 cells lacking 151P3D4 are compared to NIH-3T3
cells expressing 151P3D4, using a soft agar assay under stringent
and more permissive conditions (Song Z. et al. Cancer Res.
2000;60:6730).
[0783] To confirm the role of 151P3D4 in invasion and metastasis of
cancer cells, a well-established assay is used, e.g., a Transwell
Insert System assay (Becton Dickinson) (Cancer Res. 1999; 59:6010).
Control cells, including bladder, ovary and kidney cell lines
lacking 151P3D4 are compared to cells expressing 151P3D4. Cells are
loaded with the fluorescent dye, calcein, and plated in the top
well of the Transwell insert coated with a basement membrane
analog. Invasion is determined by fluorescence of cells in the
lower chamber relative to the fluorescence of the entire cell
population.
[0784] 151P3D4 can also play a role in cell cycle and apoptosis.
Parental cells and cells expressing 151P3D4 are compared for
differences in cell cycle regulation using a well-established BrdU
assay (Abdel-Malek Z A. J Cell Physiol. 1988, 136:247). In short,
cells are grown under both optimal (full serum) and limiting (low
serum) conditions are labeled with BrdU and stained with anti-BrdU
Ab and propidium iodide. Cells are analyzed for entry into the G1,
S, and G2M phases of the cell cycle. Alternatively, the effect of
stress on apoptosis is evaluated in control parental cells and
cells expressing 151P3D4, including normal and tumor bladder,
kidney and ovary cells. Engineered and parental cells are treated
with various chemotherapeutic agents, such as etoposide, taxol,
etc, and protein synthesis inhibitors, such as cycloheximide. Cells
are stained with annexin V-FITC and cell death is measured by FACS
analysis. The modulation of cell death by 151P3D4 can play a
critical role in regulating tumor progression and tumor load.
[0785] When 151P3D4 plays a role in cell growth, transformation,
invasion or apoptosis, it is used as a target for diagnostic,
prognostic, preventative and/or therapeutic purposes.
Example 48
[0786] Involvement in Angiogenesis
[0787] Angiogenesis or new capillary blood vessel formation is
necessary for tumor growth (Hanahan D, Folkman J. Cell. 1996,
86:353; Folkman J. Endocrinology. 1998 139:441). Based on the
effect of phsophodieseterase inhibitors on endothelial cells,
151P3D4 plays a role in angiogenesis (DeFouw L et al, Microvasc Res
2001, 62:263). Several assays have been developed to measure
angiogenesis in vitro and in vivo, such as the tissue culture
assays endothelial cell tube formation and endothelial cell
proliferation. Using these assays as well as in vitro
neo-vascularization, the role of 151P3D4 in angiogenesis,
enhancement or inhibition, is confirmed.
[0788] For example, endothelial cells engineered to express 151P3D4
are evaluated using tube formation and proliferation assays. The
effect of 151P3D4 is also confirmed in animal models in vivo. For
example, cells either expressing or lacking 151P3D4 are implanted
subcutaneously in immunocompromised mice. Endothelial cell
migration and angiogenesis are evaluated 5-15 days later using
immunohistochemistry techniques. 151P3D4 affects angiogenesis, and
it is used as a target for diagnostic, prognostic, preventative
and/or therapeutic purposes
Example 49
[0789] Involvement in Protein-Protein Interactions
[0790] Link as well as immunoglobulin motifs have been shown to
mediate interaction with other proteins, resulting in the formation
of a multi-protein complex ( ). Using immunoprecipitation
techniques as well as two yeast hybrid systems, proteins are
identified that associate with 151P3D4. Immunoprecipitates from
cells expressing 151P3D4 and cells lacking 151P3D4 are compared for
specific protein-protein associations.
[0791] Studies are performed to confirm the extent of association
of 151P3D4 with effector molecules, such as nuclear proteins,
transcription factors, kinases, phsophates etc. Studies comparing
151P3D4 positive and 151P3D4 negative cells as well as studies
comparing unstimulated/resting cells and cells treated with
epithelial cell activators, such as cytokines, growth factors and
anti-integrin Ab reveal unique interactions.
[0792] In addition, protein-protein interactions are confirmed
using two yeast hybrid methodology (Curr Opin Chem Biol. 1999,
3:64). A vector carrying a library of proteins fused to the
activation domain of a transcription factor is introduced into
yeast expressing a 151P3D4-DNA-binding domain fusion protein and a
reporter construct. Protein-protein interaction is detected by
calorimetric reporter activity. Specific association with effector
molecules and transcription factors directs one of skill to the
mode of action of 151P3D4, and thus identifies therapeutic,
prognostic, preventative and/or diagnostic targets for cancer. This
and similar assays are also used to identify and screen for small
molecules that interact with 151P3D4.
[0793] Thus it is found that 151P3D4 associates with proteins and
small molecules. Accordingly, 151P3D4 and these proteins and small
molecules are used for diagnostic, prognostic, preventative and/or
therapeutic purposes.
Example 50
[0794] Involvement in Adhesion
[0795] Cell adhesion plays a critical role in tissue colonization
and metastasis. The presence of link motif in 151P3D4 is indicative
of its role in cell adhesion. To confirm that 151P3D4 plays a role
in cell adhes control cells lacking 151P3D4 are compared to cells
expressing 151P3D4, using techniques previously described (see,
e.g., Haier et al, Br. J. Cancer. 1999, 80:1867; Lehr and Pienta,
J. Natl. Cancer Inst. 1998, 90:118). Briefly, in one embodiment,
cells labeled with a fluorescent indicator, such as calcein, are
incubated on tissue culture wells coated with media alone or with
matrix proteins. Adherent cells are detected by fluorimetric
analysis and percent adhesion is calculated. This experimental
system can be used to identify proteins, antibodies and/or small
molecules that modulate cell adhesion to extracellular matrix and
cell-cell interaction. Since cell adhesion plays a critical role in
tumor growth, progression, and, colonization, the gene involved in
this process can serves as a diagnostic, preventative and
therapeutic modality.
[0796] Throughout this application, various website data content,
publications, patent applications and patents are referenced.
(Websites are referenced by their Uniform Resource Locator, or URL,
addresses on the World Wide Web.) The disclosures of each of these
references are hereby incorporated by reference herein in their
entireties.
[0797] The present invention is not to be limited in scope by the
embodiments disclosed herein, which are intended as single
illustrations of individual aspects of the invention, and any that
are functionally equivalent are within the scope of the invention.
Various modifications to the models and methods of the invention,
in addition to those described herein, will become apparent to
those skilled in the art from the foregoing description and
teachings, and are similarly intended to fall within the scope of
the invention. Such modifications or other embodiments can be
practiced without departing from the true scope and spirit of the
invention.
4TABLE I Tissues that Express 151P3D4 When Malignant Bladder Kidney
Colon Lung Ovary Breast Stomach Uterus
[0798]
5TABLE II Amino Acid Abbreviations SINGLE LETTER THREE LETTER FULL
NAME F Phe phenylalanine L Leu leucine S Ser serine Y Tyr tyrosine
C Cys cysteine W Trp tryptophan P Pro proline H His histidine Q Gln
glutamine R Arg arginine I Ile isoleucine M Met methionine T Thr
threonine N Asn asparagine K Lys lysine V Val valine A Ala alanine
D Asp aspartic acid E Glu glutamic acid G Gly glycine
[0799]
6TABLE III Amino Acid Substitution Matrix A C D E F G H I K L M N P
Q R S T V W Y . 4 0 -2 -1 -2 0 -2 -1 -1 -1 -1 -2 -1 -1 -1 1 0 0 -3
-2 A 9 -3 -4 -2 -3 -3 -1 -3 -1 -1 -3 -3 -3 -3 -1 -1 -1 -2 -2 C 6 2
-3 -1 -1 -3 -1 -4 -3 1 -1 0 -2 0 -1 -3 -4 -3 D 5 -3 -2 0 -3 1 -3 -2
0 -1 2 0 0 -1 -2 -3 -2 E 6 -3 -1 0 -3 0 0 -3 -4 -3 -3 -2 -2 -1 1 3
F 6 -2 -4 -2 -4 -3 0 -2 -2 -2 0 -2 -3 -2 -3 G 8 -3 -1 -3 -2 1 -2 0
0 -1 -2 -3 -2 2 H 4 -3 2 1 -3 -3 -3 -3 -2 -1 3 -3 -1 I 5 -2 -1 0 -1
1 2 0 -1 -2 -3 -2 K 4 2 -3 -3 -2 -2 -2 -1 1 -2 -1 L 5 -2 -2 0 -1 -1
-1 1 -1 -1 M 6 -2 0 0 1 0 -3 -4 -2 N 7 -1 -2 -1 -1 -2 -4 -3 P 5 1 0
-1 -2 -2 -1 Q 5 -1 -1 -3 -3 -2 R 4 1 -2 -3 -2 S 5 0 -2 -2 T 4 -3 -1
V 11 2 W 7 Y Adapted from the GCG Software 9.0 BLOSUM62 amino acid
substitution matrix (block substitution matrix). The higher the
value, the more likely a substitution is found in related, natural
proteins. (See URL www.ikp.unibe.ch/manual/blosum62.html- )
[0800]
7TABLE IV (A) HLA Class I Supermotifs/Motifs POSITION POSITION
POSITION 3 (Primary C Terminus (Primary 2 (Primary Anchor) Anchor)
Anchor) SUPER- MOTIFS A1 TILVMS FWY A2 LIVMATQ IVMATL A3 VSMATLI RK
A24 YFWIVLMT FIYWLM B7 P VILFMWYA B27 RHK FYLWMIVA B44 ED FWYLIMVA
B58 ATS FWYLIVMA B62 QLIVMP FWYMIVLA MOTIFS A1 TSM Y A1 DEAS Y A2.1
LMVQIAT VLIMAT A3 LMVISATFCGD KYRHFA A11 VTMLISAGNCDF KRYH A24 YFWM
FLIW A*3101 MVTALIS RK A*3301 MVALFIST RK A*6801 AVTMSLI RK B*0702
P LMFWYAIV B*3501 P LMFWYIVA B51 P LIVFWYAM B*5301 P IMFWYALV
B*5401 P ATIVLMFWY Bolded residues are preferred, italicized
residues are less preferred: A peptide is considered motif-bearing
if it has primary anchors at each primary anchor position for a
motif or supermotif as specified in the above table.
[0801]
8TABLE IV (B) HLA Class II Supermotif 1 6 9 W, F, Y, V, .I, L A, V,
I, L, P, C, S, T A, V, I, L, C, S, T, M, Y
[0802]
9TABLE IV (C) HLA Class II Motifs MOTIFS 1.degree. anchor 1 2 3 4 5
1.degree. anchor 6 7 8 9 DR4 preferred FMYLIVW M T I VSTCPALIM MH
MH deleterious W R WDE DR1 preferred MFLIVWY PAMQ VMATSPLIC M AVM
deleterious C CH FD CWD GDE D DR7 preferred MFLIVWY M W A IVMSACTPL
M IV deleterious C G GRD N G DR3 MOTIFS 1.degree. anchor 1 2 3
1.degree. anchor 4 5 1.degree. anchor 6 motif LIVMFY D a preferred
motif LIVMFAY DNQEST KRH b preferred DR MFLIVWY VMSTACPLI
Supermotif Italicized residues indicate less preferred or
"tolerated" residues
[0803]
10TABLE IV (D) HLA Class I Supermotifs SUPER- MOTIFS POSITION: 1 2
3 4 5 6 7 8 C-terminus A1 1 1 .degree. Anchor TILVMS 2 1 .degree.
Anchor FWY A2 3 1 .degree. Anchor LIVMATQ 4 1 .degree. Anchor
LIVMAT A3 preferred 5 1 .degree. Anchor VSMATLI YFW (4/5) YFW (3/5)
YFW (4/5) P (4/5) 6 1 .degree. Anchor RK deleterious DE (3/5); DE P
(5/5) (4/5) A24 7 1 .degree. Anchor YFWIVLMT 8 1 .degree. Anchor
FIYWLM B7 preferred FWY (5/5) LIVM (3/5) 9 1 .degree. Anchor P FWY
(4/5) FWY (3/5) 10 1 .degree. Anchor VILFMWYA deleterious DE (3/5);
DE G QN DE P(5/5); (3/5) (4/5) (4/5) (4/5) G(4/5); A(3/5); QN(3/5)
B27 11 1 .degree. Anchor RHK 12 1 .degree. Anchor FYLWMIVA B44 13 1
.degree. Anchor ED 14 1 .degree. Anchor FWYLIMVA B58 15 1 .degree.
Anchor ATS 16 1 .degree. Anchor FWYLIVMA B62 17 1 .degree. Anchor
QLIVMP 18 1 .degree. Anchor FWYMIVLA Italicized residues indicate
less preferred or "tolerated"residues
[0804]
11TABLE IV (E): HLA Class I Motifs POSITION: 1 2 3 4 5 6 7 8 9
C-terminus A1 9-mer preferred deleterious GFYW DE 1 DEA RHKLIVMP
YFW A G P A DEQN YFW 2 A1 9-mer preferred deleterious GRHK A
ASTCLIVM RHKDEPYFW 3 GSTC DE PQN ASTC RHK LIVM PG DE GP 4 A1 10-mer
preferred deleterious YFW GP 5 DEAQN RHKGLIVM A DE YFWQN RHK QNA
PASTC RHKYFW GDE RHK P A 6 A1 10-mer preferred deleterious YFW RHK
STCLIVM RHKDEPYFW 7 A YFW P G PG G PRHK YFW QN 8 A2.1 9-mer
preferred deleterious YFW DEP 9 YFW DERKH STC YFW RKH A DERKH P 10
A2.1 10-mer preferred deleterious AYFW DEP 11 LVIM DE G RKHA P G
RKH FYWLVIM DERKH RKH 12 A3 preferred deleterious RHK DEP 13 YFW DE
PRHKYFW A YFW P 14 A11 preferred deleterious A DEP 15 YFW YFW A YFW
YFW A P G 16 A24 9-mer preferred deleterious YFWRHK DEG 17 DE STC G
QNP DERHK YFW G YFW AQN 18 A24 10-mer preferred deleterious 19 GDE
P QN YFWP RHK DE P A QN DEA 20 A3101 preferred deleterious RHK DEP
21 YFW DE P ADE YFW DE YFW DE AP DE 22 A3301 preferred deleterious
GP 23 YFW DE AYFW 24 A6801 preferred deleterious YFWSTC GP 25 DEG
YFWLIVM RHK YFW P A 26 B0702 preferred deleterious RHKFWY DEQNP 27
RHK DEP DE RHK DE RHK GDE RHK QN PA DE 28 B3501 preferred
deleterious FWYLIVM AGP 29 FWY G G FWY 30 B51 preferred deleterious
LIVMFWY AGPDERHKSTC 31 FWY STC FWY DE G G DEQN FWY GDE 32 B5301
preferred deleterious LIVMFWY AGPQN 33 FWY STC FWY G LIVMFWY RHKQN
FWY DE 34 B5401 preferred deleterious FWY GPQNDE 35 FWYLIVM GDESTC
LIVM RHKDE DE ALIVM QNDGE FWYAP DE 36 Italicized residues indicate
less preferred or "tolerated" residues. The information in this
Table is specific for 9-mers unless otherwise specified.
[0805]
12TABLE V Pos 1 2 3 4 5 6 7 8 9 Score SeqID v.1-A1-9mers: 151P3D4
126 I T D L T L E D Y 62.500 264 L I H P T K L T Y 25.000 14 W A D
H L S D N Y 25.000 130 T L E D Y G R Y K 18.000 57 V T L P C K F Y
R 12.500 280 L N D G A Q I A K 12.500 230 N T V P G V R N Y 12.500
153 A L D L Q G V V F 10.000 18 L S D N Y T L D H 3.750 293 F A A W
K I L G Y 2.500 155 D L Q G V V F P Y 2.500 144 G L E D D T V V V
1.800 43 E A E Q A K V F S 1.800 41 L V E A E Q A K V 1.800 213 G S
V Q Y P I T K 1.500 183 D Q D A V I A S F 1.500 119 D S D A S L V I
T 1.500 64 Y R D P T A F G S 1.250 129 L T L E D Y G R Y 1.250 201
G L D W C N A G W 1.000 181 C L D Q D A V I A 1.000 23 T L D H D R
A I H 1.000 209 W L S D G S V Q Y 1.000 308 W L A D G S V R Y 1.000
68 T A F G S G I H K 1.000 33 Q A E N G P H L L 0.900 141 V I E G L
E D D T 0.900 254 T S N F N G R F Y 0.750 117 G S D S D A S L V
0.750 255 S N F N G R F Y Y 0.625 337 F P D K K H K L Y 0.625 56 N
V T L P C K F Y 0.500 335 V G F P D K K H K 0.500 187 V I A S F D Q
L Y 0.500 158 G V V F P Y F P R 0.500 91 E V D V F V S M G 0.500
325 C S P T E A A V R 0.300 253 F T S N F N G R F 0.250 103 K T Y G
G Y Q G R 0.250 303 R C D A G W L A D 0.250 97 S M G Y H K K T Y
0.250 327 P T E A A V R F V 0.225 89 L K E V D V F V S 0.225 159 V
V F P Y F P R L 0.200 95 F V S M G Y H K K 0.200 128 D L T L E D Y
G R 0.200 324 R C S P T E A A V 0.200 40 L L V E A E Q A K 0.200
329 E A A V R F V G F 0.200 215 V Q Y P I T K P R 0.150 240 F W D K
D K S R Y 0.125 92 V D V F V S M G Y 0.125 161 F P Y F P R L G R
0.125 247 R Y D V F C F T S 0.125 148 D T V V V A L D L 0.125 345 Y
G V Y C F R A Y 0.125 343 K L Y G V Y C F R 0.100 54 G G N V T L P
C K 0.100 249 D V F C F T S N F 0.100 289 V G Q I F A A W K 0.100
272 Y D E A V Q A C L 0.090 174 F H E A Q Q A C L 0.090 138 K C E V
I E G L E 0.090 312 G S V R Y P I S R 0.075 245 K S R Y D V F C F
0.075 210 L S D G S V Q Y P 0.075 71 G S G I H K I R I 0.075 85 T S
D Y L K E V D 0.075 314 V R Y P I S R P R 0.050 219 I T K P R E P C
G 0.050 4 L L L L V L I S I 0.050 309 L A D G S V R Y P 0.050 185 D
A V I A S F D Q 0.050 176 E A Q Q A C L D Q 0.050 146 E D D T V V V
A L 0.050 270 L T Y D E A V Q A 0.050 166 R L G R Y N L N F 0.050
150 V V V A L D L Q G 0.050 107 G Y Q G R V F L K 0.050 6 L L V L I
S I C W 0.050 3 S L L L L V L I S 0.050 326 S P T E A A V R F 0.050
72 S G I H K I R I K 0.050 123 S L V I T D L T L 0.050 145 L E D D
T V V V A 0.050 251 F C F T S N F N G 0.050 232 V P G V R N Y G F
0.050 131 L E D Y G R Y K C 0.050 222 P R E P C G G Q N 0.045 156 L
Q G V V F P Y F 0.030 189 A S F D Q L Y D A 0.030 2 K S L L L L V L
I 0.030 162 P Y F P R L G R Y 0.025 316 Y P I S R P R R R 0.025 55
G N V T L P C K F 0.025 190 S F D Q L Y D A W 0.025 105 Y G G Y Q G
R V F 0.025 70 F G S G I H K I R 0.025 271 T Y D E A V Q A C 0.025
194 L Y D A W R G G L 0.025 v.2-A1-9mers: 151P3D4 34 K V D L L V P
T K 20.000 385 S L E E G L G G K 18.000 183 T L E E K R K E K
18.000 123 N T N P S R R P Y 12.500 1 M L E H T T K T F 9.000 97 S
C E G I N I S G 4.500 59 F V G S Y K L A Y 2.500 367 P A D L A G S
G Y 2.500 220 Y T E S P G G G S 2.250 238 T I A P L A A T R 2.000
208 Q A E K N M K K K 1.800 157 A S E A Y K K V C 1.350 354 K S E N
N S W Y V 1.350 226 G G S P R G L G F 1.250 302 S T Y D S L S P Y
1.250 188 R K E K A E I H Y 1.125 400 K A E N G P H L L 0.900 191 K
A E I H Y R K N 0.900 17 V V E S I R D H S 0.900 382 A I E S L E E
G L 0.900 51 A K D F G H V Q F 0.500 7 K T F P L R A L H 0.500 134
Q V P S R I F W R 0.500 296 S C P T S S S T Y 0.500 70 D G E H W T
V Y Q 0.450 105 G S F C R N K L K 0.300 103 I S G S F C R N K 0.300
373 S G Y C G A L W K 0.250 180 V T A T L E E K R 0.250 37 L L V P
T K V T G 0.200 389 G L G G K Q K D K 0.200 168 G A P H E V G W K
0.200 181 T A T L E E K R K 0.200 179 A V T A T L E E K 0.200 56 H
V Q F V G S Y K 0.200 306 S L S P Y G P R N 0.200 361 Y V E N G R P
A D 0.180 323 P S G G G G L K K 0.150 207 K Q A E K N M K K 0.150
222 E S P G G G S P R 0.150 295 S S C P T S S S T 0.150 305 D S L S
P Y G P R 0.150 83 R K D K V L L G R 0.125 68 S N D G E H W T V
0.125 101 I N I S G S F C R 0.125 169 A P H E V G W K Y 0.125 46 I
I T Q G A K D F 0.100 150 S C C P Q G H A S 0.100 154 Q G H A S E A
Y K 0.100 75 T V Y Q D E K Q R 0.100 78 Q D E K Q R K D K 0.090 384
E S L E E G L G G 0.075 133 F Q V P S R I F W 0.075 279 A S P A A W
L P L 0.075 4 H T T K T F P L R 0.050 145 K A D G G S C C P 0.050
95 V V S C E G I N I 0.050 280 S P A A W L P L R 0.050 346 R G K P
Q R K P K 0.050 265 H R P P A L S A R 0.050 377 G A L W K A I E S
0.050 44 T G I I T Q G A K 0.050 326 G G G L K K P A R 0.050 288 R
T P W T R P S S 0.050 322 S P S G G G G L K 0.050 237 K T I A P L A
A T 0.050 167 S G A P H E V G W 0.050 112 L K Y L A F L H K 0.050
121 R M N T N P S R R 0.050 303 T Y D S L S P Y G 0.050 199 N K Q L
M R L Q K 0.050 386 L E E G L G G K Q 0.045 372 G S G Y C G A L W
0.030 261 G S S A H R P P A 0.030 262 S S A H R P P A L 0.030 69 N
D G E H W T V Y 0.025 74 W T V Y Q D E K Q 0.025 21 I R D H S G Q K
M 0.025 314 N P L P N P R H S 0.025 291 W T R P S S C P T 0.025 99
E G I N I S G S F 0.025 43 V T G I I T Q G A 0.025 316 L P N P R H
S P S 0.025 47 I T Q G A K D F G 0.025 55 G H V Q F V G S Y 0.025
274 A P V P A A S P A 0.025 211 K N M K K K I D K 0.025 284 W L P L
R T P W T 0.020 241 P L A A T R A T R 0.020 190 E K A E I H Y R K
0.020 344 L A R G K P Q R K 0.020 20 S I R D H S G Q K 0.020 163 K
V C L S G A P H 0.020 155 G H A S E A Y K K 0.020 369 D L A G S G Y
C G 0.020 87 V L L G R K A V V 0.020 343 V L A R G K P Q R 0.020 12
R A L H I V V E S 0.020 203 M R L Q K Q A E K 0.020 358 N S W Y V E
N G R 0.015
[0806]
13TABLE VI Pos 1 2 3 4 5 6 7 8 9 0 Score SeqID v.1-A1-10mers:
151P3D4 91 E V D V F V S M G Y 125.000 41 L V E A E Q A K V F 9.000
33 Q A E N G P H L L V 4.500 43 E A E Q A K V F S H 4.500 254 T S N
F N G R F Y Y 3.750 117 G S D S D A S L V I 3.750 181 C L D Q D A V
I A S 2.500 23 T L D H D R A I H I 2.500 263 Y L I H P T K L T Y
2.500 324 R C S P T E A A V R 2.000 130 T L E D Y G R Y K C 1.800
144 G L E D D T V V V A 1.800 85 T S D Y L K E V D V 1.500 210 L S
D G S V Q Y P I 1.500 126 I T D L T L E D Y G 1.250 253 F T S N F N
G R F Y 1.250 327 P T E A A V R F V G 1.125 303 R C D A G W L A D G
1.000 279 C L N D G A Q I A K 1.000 309 L A D G S V R Y P I 1.000
141 V I E G L E D D T V 0.900 96 V S M G Y H K K T Y 0.750 190 S F
D Q L Y D A W R 0.500 125 V I T D L T L E D Y 0.500 201 G L D W C N
A G W L 0.500 56 N V T L P C K F Y R 0.500 128 D L T L E D Y G R Y
0.500 14 W A D H L S D N Y T 0.500 129 L T L E D Y G R Y K 0.500
186 A V I A S F D Q L Y 0.500 138 K C E V I E G L E D 0.450 93 D V
F V S M G Y H K 0.400 288 K V G Q I F A A W K 0.400 119 D S D A S L
V I T D 0.375 71 G S G I H K I R I K 0.300 325 C S P T E A A V R F
0.300 106 G G Y Q G R V F L K 0.250 64 Y R D P T A F G S G 0.250 67
P T A F G S G I H K 0.250 280 L N D G A Q I A K V 0.250 230 N T V P
G V R N Y G 0.250 212 D G S V Q Y P I T K 0.250 39 H L L V E A E Q
A K 0.200 155 D L Q G V V F P Y F 0.200 334 F V G F P D K K H K
0.200 231 T V P G V R N Y G F 0.200 152 V A L D L Q G V V F 0.200
154 L D L Q G V V F P Y 0.125 292 I F A A W K I L G Y 0.125 161 F P
Y F P R L G R Y 0.125 55 G N V T L P C K F Y 0.125 157 Q G V V F P
Y F P R 0.125 229 Q N T V P G V R N Y 0.125 311 D G S V R Y P I S R
0.125 81 W T K L T S D Y L K 0.100 53 R G G N V T L P C K 0.100 314
V R Y P I S R P R R 0.100 214 S V Q Y P I T K P R 0.100 251 F C F T
S N F N G R 0.100 159 V V F P Y F P R L G 0.100 153 A L D L Q G V V
F P 0.100 89 L K E V D V F V S M 0.090 18 L S D N Y T L D H D 0.075
2 K S L L L L V L I S 0.075 122 A S L V I T D L T L 0.075 337 F P D
K K H K L Y G 0.062 291 Q I F A A W K I L G 0.050 22 Y T L D H D R
A I H 0.050 236 R N Y G F W D K D K 0.050 145 L E D D T V V V A L
0.050 149 T V V V A L D L Q G 0.050 35 E N G P H L L V E A 0.050 57
V T L P C K F Y R D 0.050 343 K L Y G V Y C F R A 0.050 208 G W L S
D G S V Q Y 0.050 3 S L L L L V L I S I 0.050 17 H L S D N Y T L D
H 0.050 271 T Y D E A V Q A C L 0.050 307 G W L A D G S V R Y 0.050
5 L L L V L I S I C W 0.050 222 P R E P C G G Q N T 0.045 272 Y D E
A V Q A C L N 0.045 331 A V R F V G F P D K 0.040 247 R Y D V F C F
T S N 0.025 13 C W A D H L S D N Y 0.025 242 D K D K S R Y D V F
0.025 219 I T K P R E P C G G 0.025 160 V F P Y F P R L G R 0.025
238 Y G F W D K D K S R 0.025 103 K T Y G G Y Q G R V 0.025 344 L Y
G V Y C F R A Y 0.025 335 V G F P D K K H K L 0.025 270 L T Y D E A
V Q A C 0.025 54 G G N V T L P C K F 0.025 148 D T V V V A L D L Q
0.025 336 G F P D K K H K L Y 0.025 227 G G Q N T V P G V R 0.025
31 H I Q A E N G P H L 0.020 40 L L V E A E Q A K V 0.020 269 K L T
Y D E A V Q A 0.020 v.2-A1-10mers: 151P3D4 191 K A E I H Y R K N K
18.000 295 S S C P T S S S T Y 7.500 68 S N D G E H W T V Y 6.250
400 K A E N G P H L L V 4.500 105 G S F C R N K L K Y 3.750 157 A S
E A Y K K V C L 2.700 361 Y V E N G R P A D L 1.800 77 Y Q D E K Q
R K D K 1.500 372 G S G Y C G A L W K 1.500 7 K T F P L R A L H I
1.250 382 A I E S L E E G L G 0.900 385 S L E E G L G G K Q 0.900
386 L E E G L G G K Q K 0.900 183 T L E E K R K E K A 0.900 17 V V
E S I R D H S G 0.900 97 S C E G I N I S G S 0.900 133 F Q V P S R
I F W R 0.750 301 S S T Y D S L S P Y 0.750 145 K A D G G S C C P Q
0.500 123 N T N P S R R P Y H 0.500 182 A T L E E K R K E K 0.500
43 V T G I I T Q G A K 0.500 168 G A P H E V G W K Y 0.500 34 K V D
L L V P T K V 0.500 278 A A S P A A W L P L 0.500 100 G I N I S G S
F C R 0.500 237 K T I A P L A A T R 0.500 167 S G A P H E V G W K
0.500 21 I R D H S G Q K M K 0.500 180 V T A T L E E K R K 0.500 24
H S G Q K M K Q D K 0.300 321 H S P S G G G G L K 0.300 384 E S L E
E G L G G K 0.300 279 A S P A A W L P L R 0.300 354 K S E N N S W Y
V E 0.270 74 W T V Y Q D E K Q R 0.250 322 S P S G G G G L K K
0.250 250 I G H P G G R T P R 0.250 220 Y T E S P G G G S P 0.225
102 N I S G S F C R N K 0.200 75 T V Y Q D E K Q R K 0.200 342 N V
L A R G K P Q R 0.200 178 Q A V T A T L E E K 0.200 47 I T Q G A K
D F G H 0.125 152 C P Q G H A S E A Y 0.125 122 M N T N P S R R P Y
0.125 58 Q F V G S Y K L A Y 0.125 366 R P A D L A G S G Y 0.125
225 G G G S P R G L G F 0.125 54 F G H V Q F V G S Y 0.125 238 T I
A P L A A T R A 0.100 154 Q G H A S E A Y K K 0.100 284 W L P L R T
P W T R 0.100 45 G I I T Q G A K D F 0.100 13 A L H I V V E S I R
0.100 179 A V T A T L E E K R 0.100 37 L L V P T K V T G I 0.100
111 K L K Y L A F L H K 0.100 1 M L E H T T K T F P 0.090 208 Q A E
K N M K K K I 0.090 227 G S P R G L G F I F 0.075 96 V S C E G I N
I S G 0.075 240 A P L A A T R A T R 0.050 115 L A F L H K R M N T
0.050 104 S G S F C R N K L K 0.050 367 P A D L A G S G Y C 0.050
206 Q K Q A E K N M K K 0.050 302 S T Y D S L S P Y G 0.050 221 T E
S P G G G S P R 0.050 129 R P Y H F Q V P S R 0.050 94 V V V S C E
G I N I 0.050 291 W T R P S S C P T S 0.050 83 R K D K V L L G R K
0.050 274 A P V P A A S P A A 0.050 216 K I D K Y T E S P G 0.050
388 E G L G G K Q K D K 0.050 325 G G G G L K K P A R 0.050 124 T N
P S R R P Y H F 0.050 316 L P N P R H S P S G 0.050 210 E K N M K K
K I D K 0.050 70 D G E H W T V Y Q D 0.045 188 R K E K A E I H Y R
0.045 30 K Q D K K V D L L V 0.037 19 E S I R D H S G Q K 0.030 305
D S L S P Y G P R N 0.030 261 G S S A H R P P A L 0.030 262 S S A H
R P P A L S 0.030 222 E S P G G G S P R G 0.030 207 K Q A E K N M K
K K 0.030 166 L S G A P H E V G W 0.030 288 R T P W T R P S S C
0.025 198 K N K Q L M R L Q K 0.025 228 S P R G L G F I F K 0.025
357 N N S W Y V E N G R 0.025 226 G G S P R G L G F I 0.025 51 A K
D F G H V Q F V 0.025 247 A T R I G H P G G R 0.025 202 L M R L Q K
Q A E K 0.020 59 F V G S Y K L A Y S 0.020 33 K K V D L L V P T K
0.020
[0807]
14TABLE VII Pos 1 2 3 4 5 6 7 8 9 Score SeqID v.1-A2-9mers: 151P3D4
88 Y L K E V D V F V 252.512 4 L L L L V L I S I 150.931 7 L V L I
S I C W A 34.588 263 Y L I H P T K L T 34.279 5 L L L V L I S I C
29.468 151 V V A L D L Q G V 23.795 159 V V F P Y F P R L 22.339
123 S L V I T D L T L 21.362 84 L T S D Y L K E V 15.486 32 I Q A E
N G P H L 15.096 298 I L G Y D R C D A 8.446 279 C L N D G A Q I A
8.351 290 G Q I F A A W K I 7.933 291 Q I F A A W K I L 7.575 144 G
L E D D T V V V 7.483 90 K E V D V F V S M 2.634 106 G G Y Q G R V
F L 2.454 2 K S L L L L V L I 2.028 22 Y T L D H D R A I 2.022 257
F N G R F Y Y L I 1.786 186 A V I A S F D Q L 1.740 270 L T Y D E A
V Q A 1.539 209 W L S D G S V Q Y 1.405 308 W L A D G S V R Y 1.405
343 K L Y G V Y C F R 1.377 34 A E N G P H L L V 1.352 76 K I R I K
W T K L 1.328 152 V A L D L Q G V V 1.328 189 A S F D Q L Y D A
1.132 142 I E G L E D D T V 1.127 227 G G Q N T V P G V 1.044 181 C
L D Q D A V I A 0.815 41 L V E A E Q A K V 0.662 137 Y K C E V I E
G L 0.631 116 G G S D S D A S L 0.572 178 Q Q A C L D Q D A 0.504
306 A G W L A D G S V 0.490 207 A G W L S D G S V 0.490 179 Q A C L
D Q D A V 0.473 324 R C S P T E A A V 0.454 346 G V Y C F R A Y N
0.436 180 A C L D Q D A V I 0.424 276 V Q A C L N D G A 0.420 193 Q
L Y D A W R G G 0.332 284 A Q I A K V G Q I 0.316 86 S D Y L K E V
D V 0.309 39 H L L V E A E Q A 0.306 96 V S M G Y H K K T 0.306 202
L D W C N A G W L 0.299 3 S L L L L V L I S 0.260 145 L E D D T V V
V A 0.254 278 A C L N D G A Q I 0.252 281 N D G A Q I A K V 0.222
143 E G L E D D T V V 0.212 172 L N F H E A Q Q A 0.204 8 V L I S I
C W A D 0.190 117 G S D S D A S L V 0.182 268 T K L T Y D E A V
0.175 256 N F N G R F Y Y L 0.155 223 R E P C G G Q N T 0.145 246 S
R Y D V F C F T 0.142 156 L Q G V V F P Y F 0.134 81 W T K L T S D
Y L 0.129 6 L L V L I S I C W 0.127 10 I S I C W A D H L 0.116 40 L
L V E A E Q A K 0.104 24 L D H D R A I H I 0.101 287 A K V G Q I F
A A 0.092 50 F S H R G G N V T 0.092 122 A S L V I T D L T 0.088 83
K L T S D Y L K E 0.078 36 N G P H L L V E A 0.075 155 D L Q G V V
F P Y 0.075 166 R L G R Y N L N F 0.075 71 G S G I H K I R I 0.068
187 V I A S F D Q L Y 0.066 108 Y Q G R V F L K G 0.066 131 L E D Y
G R Y K C 0.066 336 G F P D K K H K L 0.061 255 S N F N G R F Y Y
0.057 15 A D H L S D N Y T 0.057 199 R G G L D W C N A 0.055 141 V
I E G L E D D T 0.055 97 S M G Y H K K T Y 0.054 121 D A S L V I T
D L 0.051 262 Y Y L I H P T K L 0.050 164 F P R L G R Y N L 0.049
251 F C F T S N F N G 0.048 1 M K S L L L L V L 0.048 288 K V G Q I
F A A W 0.043 57 V T L P C K F Y R 0.042 260 R F Y Y L I H P T
0.038 56 N V T L P C K F Y 0.036 231 T V P G V R N Y G 0.036 224 E
P C G G Q N T V 0.034 53 R G G N V T L P C 0.032 334 F V G F P D K
K H 0.030 201 G L D W C N A G W 0.030 9 L I S I C W A D H 0.030 58
T L P C K F Y R D 0.028 v.2-A2-9mers: 151P3D4 378 A L W K A I E S L
199.826 284 W L P L R T P W T 188.536 87 V L L G R K A V V 179.368
234 F I F K T I A P L 114.985 86 K V L L G R K A V 78.811 165 C L S
G A P H E V 69.552 88 L L G R K A V V V 48.478 114 Y L A F L H K R
M 22.853 231 G L G F I F K T I 19.822 201 Q L M R L Q K Q A 18.382
52 K D F G H V Q F V 15.825 57 V Q F V G S Y K L 13.624 13 A L H I
V V E S I 11.758 230 R G L G F I F K T 9.124 9 F P L R A L H I V
7.287 67 Y S N D G E H W T 5.046 354 K S E N N S W Y V 4.195 100 G
I N I S G S F C 3.757 38 L V P T K V T G I 3.569 30 K Q D K K V D L
L 3.417 95 V V S C E G I N I 1.552 110 N K L K Y L A F L 1.389 68 S
N D G E H W T V 1.362 138 R I F W R Q E K A 1.238 336 C Q G Q K H N
V L 0.888 36 D L L V P T K V T 0.848 237 K T I A P L A A T 0.833
117 F L H K R M N T N 0.788 362 V E N G R P A D L 0.706 172 E V G W
K Y Q A V 0.685 107 F C R N K L K Y L 0.617 35 V D L L V P T K V
0.608 81 K Q R K D K V L L 0.576 375 Y C G A L W K A I 0.533 93 A V
V V S C E G I 0.447 308 S P Y G P R N P L 0.446 158 S E A Y K K V C
L 0.415 27 Q K M K Q D K K V 0.357 175 W K Y Q A V T A T 0.350 33 K
K V D L L V P T 0.342 232 L G F I F K T I A 0.318 173 V G W K Y Q A
V T 0.281 289 T P W T R P S S C 0.269 242 L A A T R A T R I 0.246
279 A S P A A W L P L 0.237 29 M K Q D K K V D L 0.207 156 H A S E
A Y K K V 0.202 133 F Q V P S R I F W 0.191 370 L A G S G Y C G A
0.176 262 S S A H R P P A L 0.139 104 S G S F C R N K L 0.139 249 R
I G H P G G R T 0.133 37 L L V P T K V T G 0.127 131 Y H F Q V P S
R I 0.123 399 R K A E N G P H L 0.122 239 I A P L A A T R A 0.117
43 V T G I I T Q G A 0.117 49 Q G A K D F G H V 0.112 227 G S P R G
L G F I 0.112 299 T S S S T Y D S L 0.102 134 Q V P S R I F W R
0.096 382 A I E S L E E G L 0.092 194 I H Y R K N K Q L 0.081 268 P
A L S A R A P V 0.079 306 S L S P Y G P R N 0.075 256 R T P R A G S
S A 0.069 197 R K N K Q L M R L 0.068 400 K A E N G P H L L 0.066
270 L S A R A P V P A 0.055 111 K L K Y L A F L H 0.053 42 K V T G
I I T Q G 0.052 393 K Q K D K E R K A 0.051 295 S S C P T S S S T
0.049 10 P L R A L H I V V 0.048 200 K Q L M R L Q K Q 0.045 48 T Q
G A K D F G H 0.044 204 R L Q K Q A E K N 0.037 291 W T R P S S C P
T 0.036 240 A P L A A T R A T 0.036 277 P A A S P A A W L 0.036 328
G L K K P A R H C 0.035 261 G S S A H R P P A 0.032 337 Q G Q K H N
V L A 0.032 152 C P Q G H A S E A 0.032 325 G G G G L K K P A 0.032
274 A P V P A A S P A 0.032 266 R P P A L S A R A 0.032 236 F K T I
A P L A A 0.032 302 S T Y D S L S P Y 0.031 59 F V G S Y K L A Y
0.030 205 L Q K Q A E K N M 0.030 64 K L A Y S N D G E 0.026 343 V
L A R G K P Q R 0.025 163 K V C L S G A P H 0.023 207 K Q A E K N M
K K 0.022 16 I V V E S I R D H 0.021 102 N I S G S F C R N 0.019
116 A F L H K R M N T 0.019 368 A D L A G S G Y C 0.018 371 A G S G
Y C G A L 0.018
[0808]
15TABLE VIII Pos 1 2 3 4 5 6 7 8 9 0 Score SeqID v.1-A2-10mers:
151P3D4 83 K L T S D Y L K E V 559.894 40 L L V E A E Q A K V
484.777 343 K L Y G V Y C F R A 322.721 6 L L V L I S I C W A
106.837 3 S L L L L V L I S I 88.783 193 Q L Y D A W R G G L 36.436
4 L L L L V L I S I C 29.468 150 V V V A L D L Q G V 23.795 269 K L
T Y D E A V Q A 17.388 32 I Q A E N G P H L L 15.096 73 G I H K I R
I K W T 12.962 48 K V F S H R G G N V 10.245 297 K I L G Y D R C D
A 8.846 201 G L D W C N A G W L 6.110 255 S N F N G R F Y Y L 5.392
171 N L N F H E A Q Q A 4.968 326 S P T E A A V R F V 4.710 23 T L
D H D R A I H I 4.173 285 Q I A K V G Q I F A 3.757 209 W L S D G S
V Q Y P 3.556 158 G V V F P Y F P R L 3.551 270 L T Y D E A V Q A C
3.540 105 Y G G Y Q G R V F L 3.528 178 Q Q A C L D Q D A V 3.455
95 F V S M G Y H K K T 2.999 145 L E D D T V V V A L 2.664 9 L I S
I C W A D H L 2.447 116 G G S D S D A S L V 1.861 290 G Q I F A A W
K I L 1.510 103 K T Y G G Y Q G R V 1.406 223 R E P C G G Q N T V
1.352 130 T L E D Y G R Y K C 1.304 68 T A F G S G I H K I 1.233
144 G L E D D T V V V A 1.229 14 W A D H L S D N Y T 1.047 226 C G
G Q N T V P G V 1.044 166 R L G R Y N L N F H 0.943 142 I E G L E D
D T V V 0.943 335 V G F P D K K H K L 0.877 289 V G Q I F A A W K I
0.868 113 F L K G G S D S D A 0.800 308 W L A D G S V R Y P 0.711
280 L N D G A Q I A K V 0.710 50 F S H R G G N V T L 0.641 151 V V
L A D L Q G V V 0.551 122 A S L V I T D L T L 0.516 141 V I E G L E
D D T V 0.510 177 A Q Q A C L D Q D A 0.504 115 K G G S D S D A S L
0.488 5 L L L V L I S I C W 0.469 263 Y L I H P T K L T Y 0.343 70
F G S G I H K I R I 0.313 108 Y Q G R V F L K G G 0.304 97 S M G Y
H K K T Y G 0.296 76 K I R I K W T K L T 0.273 188 I A S F D Q L Y
D A 0.270 88 Y L K E V D V F V S 0.269 196 D A W R G G L D W C
0.266 8 V L I S I C W A D H 0.215 275 A V Q A C L N D G A 0.213 143
E G L E D D T V V V 0.212 172 L N F H E A Q Q A C 0.204 180 A C L D
Q D A V I A 0.202 90 K E V D V F V S M G 0.182 85 T S D Y L K E V D
V 0.182 277 Q A C L N D G A Q I 0.145 245 K S R Y D V F C F T 0.135
340 K K H K L Y G V Y C 0.133 206 N A G W L S D G S V 0.126 31 H I
Q A E N G P H L 0.100 309 L A D G S V R Y P I 0.099 140 E V I E G L
E D D T 0.098 288 K V G Q I F A A W K 0.095 125 V I T D L T L E D Y
0.080 153 A L D L Q G V V F P 0.075 217 Y P I T K P R E P C 0.073
181 C L D Q D A V I A S 0.069 120 S D A S L V I T D L 0.068 163 Y F
P R L G R Y N L 0.068 241 W D K D K S R Y D V 0.064 298 I L G Y D R
C D A G 0.062 33 Q A E N G P H L L V 0.062 7 L V L I S I C W A D
0.062 279 C L N D G A Q I A K 0.061 173 N F H E A Q Q A C L 0.061
179 Q A C L D Q D A V I 0.059 155 D L Q G V V F P Y F 0.058 1 M K S
L L L L V L I 0.057 42 V E A E Q A K V F S 0.056 65 R D P T A F G S
G I 0.055 286 I A K V G Q I F A A 0.055 156 L Q G V V F P Y F P
0.054 278 A C L N D G A Q I A 0.049 345 Y G V Y C F R A Y N 0.047
210 L S D G S V Q Y P I 0.046 264 L I H P T K L T Y D 0.044 261 F Y
Y L I H P T K L 0.044 283 G A Q I A K V G Q I 0.043 56 N V T L P C
K F Y R 0.042 256 N F N G R F Y Y L I 0.041 v.2-A2-10mers: 151P3D4
87 V L L G R K A V V V 179.368 67 Y S N D G E H W T V 64.221 37 L L
V P T K V T G I 40.792 86 K V L L G R K A V V 32.313 234 F I F K T
I A P L A 11.626 30 K Q D K K V D L L V 9.873 34 K V D L L V P T K
V 8.520 231 G L G F I F K T I A 7.740 200 K Q L M R L Q K Q A 6.523
204 R L Q K Q A E K N M 4.968 269 A L S A R A P V P A 4.968 57 V Q
F V G S Y K L A 4.752 2 L E H T T K T F P L 4.096 9 F P L R A L H I
V V 3.168 164 V C L S G A P H E V 2.856 381 K A I E S L E E G L
2.086 28 K M K Q D K K V D L 1.890 7 K T F P L R A L H I 1.876 373
S G Y C G A L W K A 1.790 48 T Q G A K D F G H V 1.742 94 V V V S C
E G I N I 1.552 42 K V T G I I T Q G A 1.521 276 V P A A S P A A W
L 1.304 377 G A L W K A I E S L 1.237 212 N M K K K I D K Y T 1.036
238 T I A P L A A T R A 0.683 115 L A F L H K R M N T 0.651 183 T L
E E K R K E K A 0.639 12 R A L H I V V E S I 0.604 369 D L A G S G
Y C G A 0.559 361 Y V E N G R P A D L 0.550 284 W L P L R T P W T R
0.514 133 F Q V P S R I F W R 0.510 278 A A S P A A W L P L 0.504
336 C Q G Q K H N V L A 0.504 51 A K D F G H V Q F V 0.489 230 R G
L G F I F K T I 0.479 173 V G W K Y Q A V T A 0.458 175 W K Y Q A V
T A T L 0.437 59 F V G S Y K L A Y S 0.379 353 P K S E N N S W Y V
0.359 92 K A V V V S C E G I 0.249 26 G Q K M K Q D K K V 0.247 103
I S G S F C R N K L 0.237 307 L S P Y G P R N P L 0.237 29 M K Q D
K K V D L L 0.233 241 P L A A T R A T R I 0.230 193 E I H Y R K N K
Q L 0.220 400 K A E N G P H L L V 0.216 20 S I R D H S G Q K M
0.213 106 S F C R N K L K Y L 0.188 261 G S S A H R P P A L 0.139
270 L S A R A P V P A A 0.127 378 A L W K A I E S L E 0.124 399 R K
A E N G P H L L 0.122 88 L L G R K A V V V S 0.119 226 G G S P R G
L G F I 0.112 236 F K T I A P L A A T 0.110 38 L V P T K V T G I I
0.083 362 V E N G R P A D L A 0.080 302 S T Y D S L S P Y G 0.075
155 G H A S E A Y K K V 0.072 273 R A P V P A A S P A 0.069 288 R T
P W T R P S S C 0.069 263 S A H R P P A L S A 0.069 171 H E V G W K
Y Q A V 0.069 117 F L H K R M N T N P 0.069 114 Y L A F L H K R M N
0.069 370 L A G S G Y C G A L 0.066 56 H V Q F V G S Y K L 0.064
109 K N K L K Y L A F L 0.062 201 Q L M R L Q K Q A E 0.055 207 K Q
A E K N M K K K 0.050 280 S P A A W L P L R T 0.049 334 R H C Q G Q
K H N V 0.048 46 I I T Q G A K D F G 0.047 8 T F P L R A L H I V
0.046 239 I A P L A A T R A T 0.035 233 G F I F K T I A P L 0.034
64 K L A Y S N D G E H 0.034 39 V P T K V T G I I T 0.034 151 C C P
Q G H A S E A 0.032 260 A G S S A H R P P A 0.032 324 S G G G G L K
K P A 0.032 274 A P V P A A S P A A 0.032 223 S P G G G S P R G L
0.028 35 V D L L V P T K V T 0.027 343 V L A R G K P Q R K 0.025
327 G G L K K P A R H C 0.024 16 I V V E S I R D H S 0.022 283 A W
L P L R T P W T 0.021 36 D L L V P T K V T G 0.021 172 E V G W K Y
Q A V T 0.020 194 I H Y R K N K Q L M 0.019 134 Q V P S R I F W R Q
0.019 165 C L S G A P H E V G 0.015 216 K I D K Y T E S P G 0.014
99 E G I N I S G S F C 0.013 100 G I N I S G S F C R 0.012 77 Y Q D
E K Q R K D K 0.011
[0809]
16TABLE IX Pos 1 2 3 4 5 6 7 8 9 Score SeqID v.1-A3-9mers: 151P3D4
343 K L Y G V Y C F R 135.000 40 L L V E A E Q A K 45.000 155 D L Q
G V V F P Y 24.300 166 R L G R Y N L N F 12.000 158 G V V F P Y F P
R 8.100 130 T L E D Y G R Y K 6.000 103 K T Y G G Y Q G R 4.500 159
V V F P Y F P R L 4.050 4 L L L L V L I S I 4.050 308 W L A D G S V
R Y 4.000 209 W L S D G S V Q Y 4.000 128 D L T L E D Y G R 3.600
68 T A F G S G I H K 3.000 213 G S V Q Y P I T K 2.700 153 A L D L
Q G V V F 2.000 95 F V S M G Y H K K 2.000 97 S M G Y H K K T Y
2.000 123 S L V I T D L T L 1.800 57 V T L P C K F Y R 1.350 187 V
I A S F D Q L Y 1.200 264 L I H P T K L T Y 1.200 249 D V F C F T S
N F 0.900 6 L L V L I S I C W 0.900 107 G Y Q G R V F L K 0.810 215
V Q Y P I T K P R 0.675 144 G L E D D T V V V 0.600 201 G L D W C N
A G W 0.600 161 F P Y F P R L G R 0.600 312 G S V R Y P I S R 0.540
88 Y L K E V D V F V 0.450 5 L L L V L I S I C 0.450 3 S L L L L V
L I S 0.360 56 N V T L P C K F Y 0.300 39 H L L V E A E Q A 0.300
285 Q I A K V G Q I F 0.300 332 V R F V G F P D K 0.300 126 I T D L
T L E D Y 0.300 245 K S R Y D V F C F 0.270 156 L Q G V V F P Y F
0.270 186 A V I A S F D Q L 0.270 288 K V G Q I F A A W 0.270 290 G
Q I F A A W K I 0.243 181 C L D Q D A V I A 0.200 23 T L D H D T A
I H 0.200 279 C L N D G A Q I A 0.200 298 I L G Y D R C D A 0.200
235 V R N Y G F W D K 0.180 76 K I R I K W T K L 0.180 73 G I H K I
R I K W 0.180 58 T L P C K F Y R D 0.180 228 G Q N T V P G V R
0.162 45 E Q A K V F S H R 0.162 261 F Y Y L I H P T K 0.150 291 Q
I F A A W K I L 0.150 230 N T V P G V R N Y 0.135 8 V L I S I C W A
D 0.135 75 H K I R I K W T K 0.135 333 R F V G F P D K K 0.135 129
L T L E D Y G R Y 0.135 280 L N D G A Q I A K 0.120 293 F A A W K I
L G Y 0.120 255 S N F N G R F Y Y 0.120 83 K L T S D Y L K E 0.120
263 Y L I H P T K L T 0.113 54 G G N V T L P C K 0.090 94 V F V S M
G Y H K 0.090 82 T K L T S D Y L K 0.090 253 F T S N F N G R F
0.090 346 G V Y C F R A Y N 0.090 335 V G F P D K K H K 0.075 289 V
G Q I F A A W K 0.060 269 K L T Y D E A V Q 0.060 232 V P G V R N Y
G F 0.060 234 G V R N Y G F W D 0.054 270 L T Y D E A V Q A 0.050 7
L V L I S I C W A 0.045 183 D Q D A V I A S F 0.041 148 D T V V V A
L D L 0.041 14 W A D H L S D N Y 0.040 62 K F Y R D P T A F 0.030
239 G F W D K D K S R 0.030 237 N Y G F W D K D K 0.030 151 V V A L
D L Q G V 0.030 326 S P T E A A V R F 0.030 81 W T K L T S D Y L
0.030 113 F L K G G S D S D 0.030 32 I Q A E N G P H L 0.027 342 H
K L Y G V Y C F 0.027 284 A Q I A K V G Q I 0.024 84 L T S D Y L K
E V 0.022 189 A S F D Q L Y D A 0.022 2 K S L L L L V L I 0.020 325
C S P T E A A V R 0.020 9 L I S I C W A D H 0.020 337 F P D K K H K
L Y 0.020 171 N L N F H E A Q Q 0.020 41 L V E A E Q A K V 0.020 17
H L S D N Y T L D 0.020 55 G N V T L P C K F 0.018 92 V D V F V S M
G Y 0.018 v.2-A3-9mers: 151P3D4 389 G L G G K Q K D K 45.000 34 K V
D L L V P T K 18.000 183 T L E E K R K E K 15.000 385 S L E E G L G
G K 13.500 212 N M K K K I D K Y 6.000 207 K Q A E K N M K K 5.400
378 A L W K A I E S L 4.500 231 G L G F I F K T I 4.050 121 R M N T
N P S R R 4.000 343 V L A R G K P Q R 4.000 179 A V T A T L E E K
3.000 56 H V Q F V G S Y K 3.000 13 A L H I V V E S I 2.700 59 F V
G S Y K L A Y 2.400 338 G Q K H N V L A R 2.160 26 G Q K M K Q D K
K 1.800 111 K L K Y L A F L H 1.800 134 Q V P S R I F W R 1.800 302
S T Y D S L S P Y 1.500 75 T V Y Q D E K Q R 1.000 1 M L E H T T K
T F 1.000 105 G S F C R N K L K 0.750 20 S I R D H S G Q K 0.600
112 L K Y L A F L H K 0.600 4 H T T K T F P L R 0.600 238 T I A P L
A A T R 0.600 168 G A P H E V G W K 0.540 87 V L L G R K A V V
0.450 234 F I F K T I A P L 0.450 241 P L A A T R A T R 0.400 211 K
N M K K K I D K 0.360 344 L A R G K P Q R K 0.300 165 C L S G A P H
E V 0.300 57 V Q F V G S Y K L 0.270 169 A P H E V G W K Y 0.270 7
K T F P L R A L H 0.225 88 L L G R K A V V V 0.200 373 S G Y C G A
L W K 0.200 180 V T A T L E E K R 0.200 155 G H A S E A Y K K 0.180
280 S P A A W L P L R 0.180 285 L P L R T P W T R 0.180 38 L V P T
K V T G I 0.180 30 K Q D K K V D L L 0.162 208 Q A E K N M K K K
0.150 201 Q L M R L Q K Q A 0.150 358 N S W Y V E N G R 0.150 192 A
E I H Y R K N K 0.135 95 V V S C E G I N I 0.120 284 W L P L R T P
W T 0.100 46 I I T Q G A K D F 0.100 138 R I F W R Q E K A 0.100
114 Y L A F L H K R M 0.100 181 T A T L E E K R K 0.100 137 S R I F
W R Q E K 0.090 306 S L S P Y G P R N 0.090 228 S P R G L G F I F
0.090 93 A V V V S C E G I 0.090 328 G L K K P A R H C 0.090 322 S
P S G G G G L K 0.090 113 K Y L A F L H K R 0.081 308 S P Y G P R N
P L 0.068 392 G K Q K D K E R K 0.060 73 H W T V Y Q D E K 0.060
382 A I E S L E E G L 0.060 64 K L A Y S N D G E 0.060 5 T T K T F
P L R A 0.060 163 K V C L S G A P H 0.060 125 N P S R R P Y H F
0.060 100 G I N I S G S F C 0.060 81 K Q R K D K V L L 0.054 189 K
E K A E I H Y R 0.054 237 K T I A P L A A T 0.051 55 G H V Q F V G
S Y 0.049 37 L L V P T K V T G 0.045 86 K V L L G R K A V 0.045 190
E K A E I H Y R K 0.041 199 N K Q L M R L Q K 0.040 296 S C P T S S
S T Y 0.040 10 P L R A L H I V V 0.040 101 I N I S G S F C R 0.036
36 D L L V P T K V T 0.034 323 P S G G G G L K K 0.030 103 I S G S
F C R N K 0.030 203 M R L Q K Q A E K 0.030 117 F L H K R M N T N
0.030 28 K M K Q D K K V D 0.030 123 N T N P S R R P Y 0.030 369 D
L A G S G Y C G 0.027 133 F Q V P S R I F W 0.027 84 K D K V L L G
R K 0.027 42 K V T G I I T Q G 0.020 204 R L Q K Q A E K N 0.020 25
S G Q K M K Q D K 0.020 206 Q K Q A E K N M K 0.020 244 A T R A T R
I G H 0.020 202 L M R L Q K Q A E 0.020 154 Q G H A S E A Y K 0.020
269 A L S A R A P V P 0.020 76 V Y Q D E K Q R K 0.020
[0810]
17TABLE X Pos 1 2 3 4 5 6 7 8 9 0 Score SeqID v.1-A3-10mers:
151P3D4 234 G V R N Y G F W D K 54.000 343 K L Y G V Y C F R A
40.500 279 C L N D G A Q I A K 40.000 39 H L L V E A E Q A K 30.000
288 K V G Q I F A A W K 18.000 263 Y L I H P T K L T Y 12.000 93 D
V F V S M G Y H K 9.000 331 A V R F V G F P D K 6.000 155 D L Q G V
V F P Y F 4.050 3 S L L L L V L I S I 4.050 81 W T K L T S D Y L K
3.000 106 G G Y Q G R V F L K 2.700 193 Q L Y D A W R G G L 2.700
158 G V V F P Y F P R L 2.430 186 A V I A S F D Q L Y 1.800 144 G L
E D D T V V V A 1.800 83 K L T S D Y L K E V 1.350 23 T L D H D R A
I H I 1.200 17 H L S D N Y T L D H 1.200 56 N V T L P C K F Y R
1.200 334 F V G F P D K K H K 1.000 5 L L L V L I S I C W 0.900 231
T V P G V R N Y G F 0.900 129 L T L E D Y G R Y K 0.675 125 V I T D
L T L E D Y 0.600 130 T L E D Y G R Y K C 0.600 294 A A W K I L G Y
D R 0.600 269 K L T Y D E A V Q A 0.600 251 F C F T S N F N G R
0.600 201 G L D W C N A G W L 0.540 88 Y L K E V D V F V S 0.540 4
L L L L V L I S I C 0.450 236 R N Y G F W D K D K 0.450 40 L L V E
A E Q A K V 0.450 6 L L V L I S I C W A 0.450 91 E V D V F V S M G
Y 0.360 128 D L T L E D Y G R Y 0.360 113 F L K G G S D S D A 0.300
214 S V Q Y P I T K P R 0.300 8 V L I S I C W A D H 0.300 332 V R F
V G F P D K K 0.300 166 R L G R Y N L N F H 0.300 181 C L D Q D A V
I A S 0.240 103 K T Y G G Y Q G R V 0.203 171 N L N F H E A Q Q A
0.200 67 P T A F G S G I H K 0.200 9 L I S I C W A D H L 0.180 260
R F Y Y L I H P T K 0.150 270 L T Y D E A V Q A C 0.150 284 A Q I A
K V G Q I F 0.135 297 K I L G Y D R C D A 0.135 41 L V E A E Q A K
V F 0.100 74 I H K I R I K W T K 0.090 161 F P Y F P R L G R Y
0.090 48 K V F S H R G G N V 0.090 154 L D L Q G V V F P Y 0.081 68
T A F G S G I H K I 0.068 239 G F W D K D K S R Y 0.060 324 R C S P
T E A A V R 0.060 313 S V R Y P I S R P R 0.060 153 A L D L Q G V V
F P 0.060 291 Q I F A A W K I L G 0.060 254 T S N F N G R F Y Y
0.060 209 W L S D G S V Q Y P 0.060 31 H I Q A E N G P H L 0.060
341 K H K L Y G V Y C F 0.054 255 S N F N G R F Y Y L 0.054 44 A E
Q A K V F S H R 0.054 123 S L V I T D L T L E 0.045 71 G S G I H K
I R I K 0.045 150 V V V A L D L Q G V 0.045 76 K I R I K W T K L T
0.045 309 L A D G S V R Y P I 0.041 290 G Q I F A A W K I L 0.041
285 Q I A K V G Q I F A 0.040 212 D G S V Q Y P I T K 0.036 53 R G
G N V T L P C K 0.030 94 V F V S M G Y H K K 0.030 314 V R Y P I S
R P R R 0.030 141 V I E G L E D D T V 0.030 152 V A L D L Q G V V F
0.030 86 S D Y L K E V D V F 0.030 55 G N V T L P C K F Y 0.027 157
Q G V V F P Y F P R 0.027 32 I Q A E N G P H L L 0.027 73 G I H K I
R I K W T 0.022 96 V S M G Y H K K T Y 0.022 57 V T L P C K F Y R D
0.020 210 L S D G S V Q Y P I 0.020 298 I L G Y D R C D A G 0.020
111 R V F L K G G S D S 0.020 97 S M G Y H K K T Y G 0.020 275 A V
Q A C L N D G A 0.020 253 F T S N F N G R F Y 0.020 306 A G W L A D
G S V R 0.020 79 I K W T K L T S D Y 0.020 208 G W L S D G S V Q Y
0.018 307 G W L A D G S V R Y 0.018 127 T D L T L E D Y G R 0.018
328 T E A A V R F V G F 0.018 v.2-A3-10mers: 151P3D4 111 K L K Y L
A F L H K 360.000 202 L M R L Q K Q A E K 20.000 343 V L A R G K P
Q R K 20.000 284 W L P L R T P W T R 12.000 75 T V Y Q D E K Q R K
10.000 13 A L H I V V E S I R 6.000 37 L L V P T K V T G I 4.050
100 G I N I S G S F C R 3.600 207 K Q A E K N M K K K 2.025 228 S P
R G L G F I F K 1.800 28 K M K Q D K K V D L 1.800 231 G L G F I F
K T I A 1.800 7 K T F P L R A L H I 1.350 133 F Q V P S R I F W R
1.215 182 A T L E E K R K E K 1.125 237 K T I A P L A A T R 0.900
191 K A E I H Y R K N K 0.900 102 N I S G S F C R N K 0.900 189 K E
K A E I H Y R K 0.810 372 G S G Y C G A L W K 0.600 322 S P S G G G
G L K K 0.600 342 N V L A R G K P Q R 0.600 105 G S F C R N K L K Y
0.600 129 R P Y H F Q V P S R 0.600 205 L Q K Q A E K N M K 0.600
168 G A P H E V G W K Y 0.540 180 V T A T L E E K R K 0.500 178 Q A
V T A T L E E K 0.450 87 V L L G R K A V V V 0.450 45 G I I T Q G A
K D F 0.450 77 Y Q D E K Q R K D K 0.450 179 A V T A T L E E K R
0.400 183 T L E E K R K E K A 0.300 43 V T G I I T Q G A K 0.300 33
K K V D L L V P T K 0.270 198 K N K Q L M R L Q K 0.240 269 A L S A
R A P V P A 0.200 64 K L A Y S N D G E H 0.180 94 V V V S C E G I N
I 0.180 56 H V Q F V G S Y K L 0.180 331 K P A R H C Q G Q K 0.180
74 W T V Y Q D E K Q R 0.150 234 F I F K T I A P L A 0.150 378 A L
W K A I E S L E 0.150 55 G H V Q F V G S Y K 0.135 42 K V T G I I T
Q G A 0.135 352 K P K S E N N S W Y 0.120 311 G P R N P L P N P R
0.120 88 L L G R K A V V V S 0.120 24 H S G Q K M K Q D K 0.100 204
R L Q K Q A E K N M 0.100 279 A S P A A W L P L R 0.090 34 K V D L
L V P T K V 0.090 369 D L A G S G Y C G A 0.090 112 L K Y L A F L H
K R 0.090 86 K V L L G R K A V V 0.090 389 G L G G K Q K D K E
0.090 227 G S P R G L G F I F 0.090 72 E H W T V Y Q D E K 0.090
212 N M K K K I D K Y T 0.075 391 G G K Q K D K E R K 0.060 154 Q G
H A S E A Y K K 0.060 153 P Q G H A S E A Y K 0.060 50 G A K D F G
H V Q F 0.060 152 C P Q G H A S E A Y 0.060 240 A P L A A T R A T R
0.060 361 Y V E N G R P A D L 0.060 241 P L A A T R A T R I 0.060
247 A T R I G H P G G R 0.060 328 G L K K P A R H C Q 0.060 4 H T T
K T F P L R A 0.060 211 K N M K K K I D K Y 0.054 58 Q F V G S Y K
L A Y 0.054 30 K Q D K K V D L L V 0.054 47 I T Q G A K D F G H
0.045 165 C L S G A P H E V G 0.045 386 L E E G L G G K Q K 0.045
381 K A I E S L E E G L 0.041 377 G A L W K A I E S L 0.041 12 R A
L H I V V E S I 0.041 257 T P R A G S S A H R 0.040 366 R P A D L A
G S G Y 0.040 206 Q K Q A E K N M K K 0.040 187 K R K E K A E I H Y
0.036 384 E S L E E G L G G K 0.030 136 P S R I F W R Q E K 0.030
295 S S C P T S S S T Y 0.030 301 S S T Y D S L S P Y 0.030 201 Q L
M R L Q K Q A E 0.030 238 T I A P L A A T R A 0.030 321 H S P S G G
G G L K 0.030 38 L V P T K V T G I I 0.027 167 S G A P H E V G W K
0.027 92 K A V V V S C E G I 0.027 134 Q V P S R I F W R Q 0.027
337 Q G Q K H N V L A R 0.024 1 M L E H T T K T F P 0.020 117 F L H
K R M N T N P 0.020 20 S I R D H S G Q K M 0.020 25 S G Q K M K Q D
K K 0.020
[0811]
18TABLE XI Pos 1 2 3 4 5 6 7 8 9 Score SeqID v.1-A11-9mers: 151P3D4
158 G V V F P Y F P R 5.400 107 G Y Q G R V F L K 3.600 95 F V S M
G Y H K K 2.000 103 K T Y G G Y Q G R 1.200 57 V T L P C K F Y R
0.900 333 R F V G F P D K K 0.900 68 T A F G S G I H K 0.800 261 F
Y Y L I H P T K 0.800 94 V F V S M G Y H K 0.600 40 L L V E A E Q A
K 0.600 343 K L Y G V Y C F R 0.480 228 G Q N T V P G V R 0.360 315
R Y P I S R P R R 0.240 237 N Y G F W D K D K 0.200 213 G S V Q Y P
I T K 0.180 161 F P Y F P R L G R 0.160 239 G F W D K D K S R 0.120
215 V Q Y P I T K P R 0.120 280 L N D G A Q I A K 0.080 75 H K I R
I K W T K 0.060 82 T K L T S D Y L K 0.060 54 G G N V T L P C K
0.060 288 K V G Q I F A A W 0.060 290 G Q I F A A W K I 0.054 128 D
L T L E D Y G R 0.048 130 T L E D Y G R Y K 0.040 252 C F T S N F N
G R 0.040 332 V R F V G F P D K 0.040 235 V R N Y G F W D K 0.040
159 V V F P Y F P R L 0.040 312 G S V R Y P I S R 0.036 45 E Q A K
V F S H R 0.036 186 A V I A S F D Q L 0.030 7 L V L I S I C W A
0.030 73 G I H K I R I K W 0.024 166 R L G R Y N L N F 0.024 270 L
T Y D E A V Q A 0.020 335 V G F P D K K H K 0.020 151 V V A L D L Q
G V 0.020 289 V G Q I F A A W K 0.020 41 L V E A E Q A K V 0.020
307 G W L A D G S V R 0.018 234 G V R N Y G F W D 0.018 129 L T L E
D Y G R Y 0.015 201 G L D W C N A G W 0.012 346 G V Y C F R A Y N
0.012 169 R Y N L N F H E A 0.012 4 L L L L V L I S I 0.012 249 D V
F C F T S N F 0.012 6 L L V L I S I C W 0.012 144 G L E D D T V V V
0.012 300 G Y D R C D A G W 0.012 76 K I R I K W T K L 0.012 48 K V
F S H R G G N 0.012 62 K F Y R D P T A F 0.012 111 R V F L K G G S
D 0.012 123 S L V I T D L T L 0.012 344 L Y G V Y C F R A 0.012 93
D V F V S M G Y H 0.012 253 F T S N F N G R F 0.010 56 N V T L P C
K F Y 0.010 334 F V G F P D K K H 0.010 126 I T D L T L E D Y 0.010
81 W T K L T S D Y L 0.010 148 D T V V V A L D L 0.009 284 A Q I A
K V G Q I 0.009 264 L I H P T K L T Y 0.008 295 A W K I L G Y D R
0.008 316 Y P I S R P R R R 0.006 178 Q Q A C L D Q D A 0.006 324 R
C S P T E A A V 0.006 150 V V V A L D L Q G 0.006 276 V Q A C L N D
G A 0.006 32 I Q A E N G P H L 0.006 331 A V R F V G F P D 0.006
262 Y Y L I H P T K L 0.006 39 H L L V E A E Q A 0.006 156 L Q G V
V F P Y F 0.006 336 G F P D K K H K L 0.006 84 L T S D Y L K E V
0.005 20 D N Y T L D H D R 0.005 9 L I S I C W A D H 0.004 104 T Y
G G Y Q G R V 0.004 325 C S P T E A A V R 0.004 293 F A A W K I L G
Y 0.004 291 Q I F A A W K I L 0.004 256 N F N G R F Y Y L 0.004 164
F P R L G R Y N L 0.004 232 V P G V R N Y G F 0.004 298 I L G Y D R
C D A 0.004 209 W L S D G S V Q Y 0.004 153 A L D L Q G V V F 0.004
279 C L N D G A Q I A 0.004 286 I A K V G Q I F A 0.004 194 L Y D A
W R G G L 0.004 191 F D Q L Y D A W R 0.004 181 C L D Q D A V I A
0.004 31 H I Q A E N G P H 0.004 308 W L A D G S V R Y 0.004 88 Y L
K E V D V F V 0.004 v.2-A11-9mers: 151P3D4 34 K V D L L V P T K
6.000 207 K Q A E K N M K K 3.600 56 H V Q F V G S Y K 2.000 179 A
V T A T L E E K 2.000 26 G Q K M K Q D K K 1.800 134 Q V P S R I F
W R 1.200 338 G Q K H N V L A R 0.720 389 G L G G K Q K D K 0.600
168 G A P H E V G W K 0.600 211 K N M K K K I D K 0.480 75 T V Y Q
D E K Q R 0.400 385 S L E E G L G G K 0.400 76 V Y Q D E K Q R K
0.400 20 S I R D H S G Q K 0.400 113 K Y L A F L H K R 0.360 121 R
M N T N P S R R 0.240 322 S P S G G G G L K 0.200 344 L A R G K P Q
R K 0.200 4 H T T K T F P L R 0.200 183 T L E E K R K E K 0.200 180
V T A T L E E K R 0.200 155 G H A S E A Y K K 0.120 285 L P L R T P
W T R 0.120 208 Q A E K N M K K K 0.100 181 T A T L E E K R K 0.100
238 T I A P L A A T R 0.080 343 V L A R G K P Q R 0.080 373 S G Y C
G A L W K 0.080 112 L K Y L A F L H K 0.080 84 K D K V L L G R K
0.060 105 G S F C R N K L K 0.060 392 G K Q K D K E R K 0.060 7 K T
F P L R A L H 0.060 163 K V C L S G A P H 0.060 86 K V L L G R K A
V 0.045 192 A E I H Y R K N K 0.045 280 S P A A W L P L R 0.040 95
V V S C E G I N I 0.040 199 N K Q L M R L Q K 0.040 59 F V G S Y K
L A Y 0.040 101 I N I S G S F C R 0.036 111 K L K Y L A F L H 0.036
189 K E K A E I H Y R 0.036 22 R D H S G Q K M K 0.030 346 R G K P
Q R K P K 0.030 203 M R L Q K Q A E K 0.030 44 T G I I T Q G A K
0.030 137 S R I F W R Q E K 0.030 256 R T P R A G S S A 0.030 93 A
V V V S C E G I 0.030 83 R K D K V L L G R 0.024 120 K R M N T N P
S R 0.024 138 R I F W R Q E K A 0.024 57 V Q F V G S Y K L 0.024
374 G Y C G A L W K A 0.024 5 T T K T F P L R A 0.020 25 S G Q K M
K Q D K 0.020 332 P A R H C Q G Q K 0.020 38 L V P T K V T G I
0.020 206 Q K Q A E K N W K 0.020 244 A T R A T R I G H 0.020 302 S
T Y D S L S P Y 0.020 73 H W T V Y Q D E K 0.020 154 Q G H A S E A
Y K 0.020 81 K Q R K D K V L L 0.018 133 F Q V P S R I F W 0.018 48
T Q G A K D F G H 0.018 30 K Q D K K V D L L 0.018 326 G G G L K K
P A R 0.012 251 G H P G G R T P R 0.012 176 K Y Q A V T A T L 0.012
190 E K A E I H Y R K 0.012 78 Q D E K Q R K D K 0.010 43 V T G I I
T Q G A 0.010 387 E E G L G G K Q K 0.009 241 P L A A T R A T R
0.008 130 P Y H F Q V P S R 0.008 378 A L W K A I E S L 0.008 358 N
S W Y V E N G R 0.008 196 Y R K N K Q L M R 0.008 234 F I F K T I A
P L 0.008 14 L H I V V E S I R 0.006 391 G G K Q K D K E R 0.006
340 K H N V L A R G K 0.006 248 T R I G H P G G R 0.006 87 V L L G
R K A V V 0.006 172 E V G W K Y Q A V 0.006 400 K A E N G P H L L
0.006 352 K P K S E N N S W 0.006 42 K V T G I I T Q G 0.006 228 S
P R G L G F I F 0.006 231 G L G F I F K T I 0.006 336 C Q G Q K H N
V L 0.006 266 R P P A L S A R A 0.006 237 K T I A P L A A T 0.005
323 P S G G G G L K K 0.004 229 P R G L G F I F K 0.004 169 A P H E
V G W K Y 0.004 308 S P Y G P R N P L 0.004 106 S F C R N K L K Y
0.004
[0812]
19TABLE XII Pos 1 2 3 4 5 6 7 8 9 0 Score SeqID v.1-A11-10mers:
151P3D4 234 G V R N Y G F W D K 12.000 288 K V G Q I F A A W K
6.000 93 D V F V S M G Y H K 2.400 81 W T K L T S D Y L K 2.000 331
A V R F V G F P D K 2.000 260 R F Y Y L I H P T K 1.200 56 N V T L
P C K F Y R 1.200 334 F V G F P D K K H K 1.000 279 C L N D G A Q I
A K 0.800 39 H L L V E A E Q A K 0.600 106 G G Y Q G R V F L K
0.360 94 V F V S M G Y H K K 0.300 67 P T A F G S G I H K 0.200 214
S V Q Y P I T K P R 0.200 294 A A W K I L G Y D R 0.160 129 L T L E
D Y G R Y K 0.150 236 R N Y G F W D K D K 0.120 324 R C S P T E A A
V R 0.120 48 K V F S H R G G N V 0.120 158 G V V F P Y F P R L
0.090 160 V F P Y F P R L G R 0.080 251 F C F T S N F N G R 0.080
343 K L Y G V Y C F R A 0.072 53 R G G N V T L P C K 0.060 103 K T
Y G G Y Q G R V 0.060 74 I H K I R I K W T K 0.040 190 S F D Q L Y
D A W R 0.040 231 T V P G V R N Y G F 0.040 332 V R F V G F P D K K
0.040 313 S V R Y P I S R P R 0.040 186 A V I A S F D Q L Y 0.030
150 V V V A L D L Q G V 0.030 315 R Y P I S R P R R R 0.024 275 A V
Q A C L N D G A 0.020 69 A F G S G I H K I R 0.020 151 V V A L D L
Q G V V 0.020 157 Q G V V F P Y F P R 0.018 297 K I L G Y D R C D A
0.018 22 Y T L D H D R A I H 0.015 290 G Q I F A A W K I L 0.013
102 K K T Y G G Y Q G R 0.012 127 T D L T L E D Y G R 0.012 227 G G
Q N T V P G V R 0.012 111 R V F L K G G S D S 0.012 136 R Y K C E V
I E G L 0.012 300 G Y D R C D A G W L 0.012 44 A E Q A K V F S H R
0.012 91 E V D V F V S M G Y 0.012 239 G F W D K D K S R Y 0.012
263 Y L I H P T K L T Y 0.012 144 G L E D D T V V V A 0.012 212 D G
S V Q Y P I T K 0.012 166 R L G R Y N L N F H 0.012 5 L L L V L I S
I C W 0.012 3 S L L L L V L I S I 0.012 201 G L D W C N A G W L
0.012 99 G Y H K K T Y G G Y 0.012 269 K L T Y D E A V Q A 0.012 41
L V E A E Q A K V F 0.010 284 A Q I A K V G Q I F 0.009 306 A G W L
A D G S V R 0.008 314 V R Y P I S R P R R 0.008 23 T L D H D R A I
H I 0.008 17 H L S D N Y T L D H 0.008 261 F Y Y L I H P T K L
0.008 285 Q I A K V G Q I F A 0.008 193 Q L Y D A W R G G L 0.008
71 G S G I H K I R I K 0.006 342 H K L Y G V Y C F R 0.006 7 L V L
I S I C W A D 0.006 124 L V I T D L T L E D 0.006 286 I A K V G Q I
F A A 0.006 6 L L V L I S I C W A 0.006 149 T V V V A L D L Q G
0.006 178 Q Q A C L D Q D A V 0.006 32 I Q A E N G P H L L 0.006 8
V L I S I C W A D H 0.006 40 L L V E A E Q A K V 0.006 283 G A Q I
A K V G Q I 0.006 177 A Q Q A C L D Q D A 0.006 83 K L T S D Y L K
E V 0.006 333 R F V G F P D K K H 0.005 19 S D N Y T L D H D R
0.004 9 L I S I C W A D H L 0.004 188 I A S F D Q L Y D A 0.004 163
Y F P R L G R Y N L 0.004 256 N F N G R F Y Y L I 0.004 171 N L N F
H E A Q Q A 0.004 271 T Y D E A V Q A C L 0.004 125 V I T D L T L E
D Y 0.004 33 Q A E N G P H L L V 0.004 31 H I Q A E N G P H L 0.004
292 I F A A W K I L G Y 0.004 113 F L K G G S D S D A 0.004 68 T A
F G S G I H K I 0.004 309 L A D G S V R Y P I 0.004 161 F P Y F P R
L G R Y 0.004 238 Y G F W D K D K S R 0.004 141 V I E G L E D D T V
0.004 336 G F P D K K H K L Y 0.003 v.2-A11-10mers: 151P3D4 75 T V
Y Q D E K Q R K 4.000 111 K L K Y L A F L H K 2.400 43 V T G I I T
Q G A K 1.000 207 K Q A E K N M K K K 0.900 237 K T I A P L A A T R
0.900 182 A T L E E K R K E K 0.750 100 G I N I S G S F C R 0.720
205 L Q K Q A E K N M K 0.600 342 N V L A R G K P Q R 0.600 331 K P
A R H C Q G Q K 0.600 133 F Q V P S R I F W R 0.540 180 V T A T L E
E K R K 0.500 343 V L A R G K P Q R K 0.400 228 S P R G L G F I F K
0.400 322 S P S G G G G L K K 0.400 202 L M R L Q K Q A E K 0.400
179 A V T A T L E E K R 0.400 189 K E K A E I H Y R K 0.360 178 Q A
V T A T L E E K 0.300 191 K A E I H Y R K N K 0.300 77 Y Q D E K Q
R K D K 0.300 198 K N K Q L M R L Q K 0.240 129 R P Y H F Q V P S R
0.240 247 A T R I G H P G G R 0.200 195 H Y R K N K Q L M R 0.160
284 W L P L R T P W T R 0.160 74 W T V Y Q D E K Q R 0.150 372 G S
G Y C G A L W K 0.120 311 G P R N P L P N P R 0.120 7 K T F P L R A
L H I 0.120 55 G H V Q F V G S Y K 0.090 33 K K V D L L V P T K
0.090 86 K V L L G R K A V V 0.090 13 A L H I V V E S I R 0.080 391
G G K Q K D K E R K 0.060 153 P Q G H A S E A Y K 0.060 83 R K D K
V L L G R K 0.060 94 V V V S C E G I N I 0.060 34 K V D L L V P T K
V 0.060 42 K V T G I I T Q G A 0.060 240 A P L A A T R A T R 0.060
206 Q K Q A E K N M K K 0.040 154 Q G H A S E A Y K K 0.040 102 N I
S G S F C R N K 0.040 257 T P R A G S S A H R 0.040 56 H V Q F V G
S Y K L 0.040 30 K Q D K K V D L L V 0.036 386 L E E G L G G K Q K
0.030 256 R T P R A G S S A H 0.030 47 I T Q G A K D F G H 0.030
120 K R M N T N P S R R 0.024 25 S G Q K M K Q D K K 0.020 38 L V P
T K V T G I I 0.020 167 S G A P H E V G W K 0.020 321 H S P S G G G
G L K 0.020 4 H T T K T F P L R A 0.020 24 H S G Q K M K Q D K
0.020 361 Y V E N G R P A D L 0.020 200 K Q L M R L Q K Q A 0.013
188 R K E K A E I H Y R 0.012 325 G G G G L K K P A R 0.012 64 K L
A Y S N D G E H 0.012 210 E K N M K K K I D K 0.012 400 K A E N G P
H L L V 0.012 72 E H W T V Y Q D E K 0.012 231 G L G F I F K T I A
0.012 28 K M K Q D K K V D L 0.012 221 T E S P G G G S P R 0.012
168 G A P H E V G W K Y 0.012 104 S G S F C R N K L K 0.010 123 N T
N P S R R P Y H 0.010 21 I R D H S G Q K M K 0.010 345 A R G K P Q
R K P K 0.010 45 G I I T Q G A K D F 0.009 19 E S I R D H S G Q K
0.009 26 G Q K M K Q D K K V 0.009 113 K Y L A F L H K R M 0.009
233 G F I F K T I A P L 0.009 92 K A V V V S C E G I 0.009 12 R A L
H I V V E S I 0.009 377 G A L W K A I E S L 0.009 384 E S L E E G L
G G K 0.009 381 K A I E S L E E G L 0.009 82 Q R K D K V L L G R
0.008 234 F I F K T I A P L A 0.008 337 Q G Q K H N V L A R 0.008
357 N N S W Y V E N G R 0.008 112 L K Y L A F L H K R 0.008 374 G Y
C G A L W K A I 0.006 163 K V C L S G A P H E 0.006 9 F P L R A L H
I V V 0.006 352 K P K S E N N S W Y 0.006 50 G A K D F G H V Q F
0.006 336 C Q G Q K H N V L A 0.006 37 L L V P T K V T G I 0.006
204 R L Q K Q A E K N M 0.006 58 Q F V G S Y K L A Y 0.006 57 V Q F
V G S Y K L A 0.006 366 R P A D L A G S G Y 0.006 273 R A P V P A A
S P A 0.006
[0813]
20TABLE XIII Pos 1 2 3 4 5 6 7 8 9 Score Seq ID v.1-A24-9mers:
151P3D4 262 Y Y L I H P T K L 330.000 194 L Y D A W R G G L 200.000
87 D Y L K E V D V F 150.000 336 G F P D K K H K L 39.600 256 N F N
G R F Y Y L 36.000 62 K F Y R D P T A F 20.000 169 R Y N L N F H E
A 19.800 247 R Y D V F C F T S 10.000 76 K I R I K W T K L 8.800
148 D T V V V A L D L 8.400 271 T Y D E A V Q A C 7.200 186 A V I A
S F D Q L 7.200 10 I S I C W A D H L 6.000 33 Q A E N G P H L L
6.000 123 S L V I T D L T L 6.000 159 V V F P Y F P R L 5.760 121 D
A S L V I T D L 5.600 133 D Y G R Y K C E V 5.500 69 A F G S G I H
K I 5.500 344 L Y G V Y C F R A 5.000 300 G Y D R C D A G W 5.000
21 N Y T L D H D R A 5.000 104 T Y G G Y Q G R V 5.000 32 I Q A E N
G P H L 4.800 116 G G S D S D A S L 4.800 245 K S R Y D V F C F
4.000 164 F P R L G R Y N L 4.000 166 R L G R Y N L N F 4.000 81 W
T K L T S D Y L 4.000 291 Q I F A A W K I L 4.000 106 G G Y Q G R V
F L 4.000 55 G N V T L P C K F 3.960 2 K S L L L L V L I 3.600 156
L Q G V V F P Y F 3.360 285 Q I A K V G Q I F 3.360 183 D Q D A V I
A S F 2.800 329 E A A V R F V G F 2.400 326 S P T E A A V R F 2.400
4 L L L L V L I S I 2.100 249 D V F C F T S N F 2.000 232 V P G V R
N Y G F 2.000 105 Y G G Y Q G R V F 2.000 253 F T S N F N G R F
2.000 153 A L D L Q G V V F 2.000 22 Y T L D H D R A I 1.800 180 A
C L D Q D A V I 1.800 290 G Q I F A A W K I 1.650 284 A Q I A K V G
Q I 1.500 278 A C L N D G A Q I 1.500 315 R Y P I S R P R R 1.500
260 R F Y Y L I H P T 1.200 36 R Y K C E V I E G 1.100 134 Y G R Y
K C E V I 1.000 71 G S G I H K I R I 1.000 257 F N G R F Y Y L I
1.000 66 D P T A F G S G I 1.000 163 Y F P R L G R Y N 0.900 272 Y
D E A V Q A C L 0.840 112 V F L K G G S D S 0.750 216 Q Y P I T K P
R E 0.750 107 G Y Q G R V F L K 0.750 173 N F H E A Q Q A C 0.720
261 F Y Y L I H P T K 0.700 537 Y K C E V I E G L 0.672 190 S F D Q
L Y D A W 0.600 250 V F C F T S N F N 0.600 162 P Y F P R L G R Y
0.600 63 F Y R D P T A F G 0.600 16 D H L S D N Y T L 0.600 174 F H
E A Q Q A C L 0.600 146 E D D T V V V A L 0.560 99 G Y H K K T Y G
G 0.500 237 N Y G F W D K D K 0.500 49 V F S H R G G N V 0.500 1 M
K S L L L L V L 0.480 28 R A I H I Q A E N 0.462 51 S H R G G N V T
L 0.400 243 K D K S R Y D V F 0.400 202 L D W C N A G W L 0.400 301
Y D R C D A G W L 0.400 288 K V G Q I F A A W 0.336 90 K E V D V F
V S M 0.302 342 H K L Y G V Y C F 0.300 53 R G G N V T L P C 0.280
324 R C S P T E A A V 0.240 42 V E A E Q A K V F 0.240 80 K W T K L
T S D Y 0.240 152 V A L D L Q G V V 0.216 279 C L N D G A Q I A
0.216 155 D L Q G V V F P Y 0.210 122 A S L V I T D L T 0.210 6 L L
V L I S I C W 0.210 199 R G G L D W C N A 0.200 48 K V F S H R G G
N 0.200 320 R P R R R C S P T 0.200 115 K G G S D S D A S 0.200 78
R I K W T K L T S 0.200 36 N G P H L L V E A 0.198 345 Y G V Y C F
R A Y 0.180 129 L T L E D Y G R Y 0.180 v.2-A24-9mers: 151P3D4 176
K Y Q A V T A T L 840.000 195 H Y R K N K Q L M 30.000 132 H F Q V
P S R I F 15.000 400 K A E N G P H L L 12.000 360 W Y V E N G R P A
9.000 81 K Q R K D K V L L 8.000 30 K Q D K K V D L L 8.000 8 T F P
L R A L H I 7.500 382 A I E S L E E G L 7.200 279 A S P A A W L P L
6.000 321 H S P S G G G G L 6.000 374 G Y C G A L W K A 5.500 104 S
G S F C R N K L 5.280 66 A Y S N D G E H W 5.000 336 C Q G Q K H N
V L 4.800 308 S P Y G P R N P L 4.800 57 V Q F V G S Y K L 4.400 99
E G I N I S G S F 4.200 107 F C R N K L K Y L 4.000 234 F I F K T I
A P L 4.000 378 A L W K A I E S L 4.000 109 R N K L K Y L A F 4.000
299 T S S S T Y D S L 4.000 371 A G S G Y C G A L 4.000 262 S S A H
R P P A L 4.000 1 M L E H T T K T F 3.000 226 G G S P R G L G F
2.400 228 S P R G L G F I F 2.400 46 I I T Q G A K D F 2.000 125 N
P S R R P Y H F 2.000 231 G L G F I F K T I 1.680 113 K Y L A F L H
K R 1.650 227 G S P R G L G F I 1.500 38 L V P T K V T G I 1.500 93
A V V V S C E G I 1.500 39 V P T K V T G I I 1.400 13 A L H I V V E
S I 1.400 375 Y C G A L W K A I 1.200 219 K Y T E S P G G G 1.200
197 R K N K Q L M R L 1.200 76 V Y Q D E K Q R K 1.080 95 V V S C E
G I N I 1.000 242 L A A T R A T R I 1.000 399 R K A E N G P H L
0.960 58 Q F V G S Y K L A 0.750 116 A F L H K R M N T 0.750 29 M K
Q D K K V D L 0.720 160 A Y K K V C L S G 0.700 235 I F K T I A P L
A 0.700 114 Y L A F L H K R M 0.600 362 V E N G R P A D L 0.600 110
N K L K Y L A F L 0.600 303 T Y D S L S P Y G 0.600 80 E K Q R K D
K V L 0.600 106 S F C R N K L K Y 0.550 205 L Q K Q A E K N M 0.500
62 S Y K L A Y S N D 0.500 12 R A L H I V V E S 0.462 3 E H T T K T
F P L 0.400 158 S E A Y K K V C L 0.400 277 P A A S P A A W L 0.400
224 P G G G S P R G L 0.400 194 I H Y R K N K Q L 0.400 6 T K T F P
L R A L 0.400 266 R P P A L S A R A 0.360 191 K A E I H Y R K N
0.330 204 R L Q K Q A E K N 0.330 230 R G L G F I F K T 0.330 86 K
V L L G R K A V 0.300 354 K S E N N S W Y V 0.300 288 R T P W T R P
S S 0.300 142 R Q E K A D G G S 0.300 237 K T I A P L A A T 0.300
256 R T P R A G S S A 0.300 393 K Q K D K E R K A 0.264 352 K P K S
E N N S W 0.240 138 R I F W R Q E K A 0.220 283 A W L P L R T P W
0.216 17 V V E S I R D H S 0.210 293 R P S S C P T S S 0.200 249 R
I G H P G G R T 0.200 51 A K D F G H V Q F 0.200 129 R P Y H F Q V
P S 0.200 169 A P H E V G W K Y 0.185 316 L P N P R H S P S 0.180
67 Y S N D G E H W T 0.180 201 Q L M R L Q K Q A 0.180 133 F Q V P
S R I F W 0.180 123 N T N P S R R P Y 0.180 274 A P V P A A S P A
0.180 314 N P L P N P R H S 0.180 43 V T G I I T Q G A 0.168 152 C
P Q G H A S E A 0.165 356 E N N S W Y V E N 0.165 377 G A L W K A I
E S 0.165 335 H C Q G Q K H N V 0.150 94 V V V S C E G I N 0.150
100 G I N I S G S F C 0.150 87 V L L G R K A V V 0.150 239 I A P L
A A T R A 0.150
[0814]
21TABLE XIV Pos 1 2 3 4 5 6 7 8 9 0 Score Seq ID v.1-A24-10mers:
151P3D4 136 R Y K C E V I E G L 560.000 271 T Y D E A V Q A C L
336.000 261 F Y Y L I H P T K L 220.000 300 G Y D R C D A G W L
200.000 104 T Y G G Y Q G R V F 100.000 133 D Y G R Y K C E V I
50.000 21 N Y T L D H D R A I 50.000 163 Y F P R L G R Y N L 30.000
173 N F H E A Q Q A C L 24.000 247 R Y D V F C F T S N 12.000 87 D
Y L K E V D V F V 10.500 252 C F T S N F N G R F 10.000 115 K G G S
D S D A S L 8.000 80 K W T K L T S D Y L 8.000 256 N F N G R F Y Y
L I 7.500 262 Y Y L I H P T K L T 7.500 158 G V V F P Y F P R L
7.200 185 D A V I A S F D Q L 7.200 344 L Y G V Y C F R A Y 6.000
122 A S L V I T D L T L 6.000 63 F Y R D P T A F G S 6.000 31 H I Q
A E N G P H L 6.000 290 G Q I F A A W K I L 6.000 237 N Y G F W D K
D K S 5.500 335 V G F P D K K H K L 5.280 155 D L Q G V V F P Y F
5.040 284 A Q I A K V G Q I F 5.040 99 G Y H K K T Y G G Y 5.000 32
I Q A E N G P H L L 4.800 255 S N F N G R F Y Y L 4.800 193 Q L Y D
A W R G G L 4.800 105 Y G G Y Q G R V F L 4.000 50 F S H R G G N V
T L 4.000 201 G L D W C N A G W L 4.000 9 L I S I C W A D H L 4.000
54 G G N V T L P C K F 3.960 152 V A L D L Q G V V F 3.600 41 L V E
A E Q A K V F 3.000 231 T V P G V R N Y G F 3.000 325 C S P T E A A
V R F 3.000 3 S L L L L V L I S I 2.100 289 V G Q I F A A W K I
1.650 169 R Y N L N F H E A Q 1.500 283 G A Q I A K V G Q I 1.500
315 R Y P I S R P R R R 1.500 309 L A D G S V R Y P I 1.400 210 L S
D G S V Q Y P I 1.400 107 G Y Q G R V F L K G 1.386 68 T A F G S G
I H K I 1.100 23 T L D H D R A I H I 1.000 277 Q A C L N D G A Q I
1.000 117 G S D S D A S L V I 1.000 70 F G S G I H K I R I 1.000
179 Q A C L D Q D A V I 1.000 336 G F P D K K H K L Y 0.900 216 Q Y
P I T K P R E P 0.825 162 P Y F P R L G R Y N 0.720 145 L E D D T V
V V A L 0.672 75 H K I R I K W T K L 0.660 239 G F W D K D K S R Y
0.600 49 V F S H R G G N V T 0.600 120 S D A S L V I T D L 0.560
147 D D T V V V A L D L 0.560 182 L D Q D A V I A S F 0.504 194 L Y
D A W R G G L D 0.500 292 I F A A W K I L G Y 0.500 15 A D H L S D
N Y T L 0.400 341 K H K L Y G V Y C F 0.400 2 K S L L L L V L I S
0.360 245 K S R Y D V F C F T 0.336 65 R D P T A F G S G I 0.300
297 K I L G Y D R C D A 0.300 248 Y D V F C F T S N F 0.300 328 T E
A A V R F V G F 0.240 221 K P R E P C G G Q N 0.240 72 S G I H K I
R I K W 0.231 83 K L T S D Y L K E V 0.220 177 A Q Q A C L D Q D A
0.216 140 E V I E G L E D D T 0.216 5 L L L V L I S I C W 0.210 269
K L T Y D E A V Q A 0.200 61 C K F Y R D P T A F 0.200 48 K V F S H
R G G N V 0.200 343 K L Y G V Y C F R A 0.200 103 K T Y G G Y Q G R
V 0.200 76 K I R I K W T K L T 0.200 111 R V F L K G G S D S 0.200
244 D K S R Y D V F C F 0.200 242 D K D K S R Y D V F 0.200 86 S D
Y L K E V D V F 0.200 130 T L E D Y G R Y K C 0.198 40 L L V E A E
Q A K V 0.198 180 A C L D Q D A V I A 0.180 278 A C L N D G A Q I A
0.180 275 A V Q A C L N D G A 0.180 4 L L L L V L I S I C 0.180 143
E G L E D D T V V V 0.180 150 V V V A L D L Q G V 0.180 144 G L E D
D T V V V A 0.180 200 G G L D W C N A G W 0.180 v.2-A24-10mers:
151P3D4 113 K Y L A F L H K R M 90.000 374 G Y C G A L W K A I
60.000 233 G F I F K T I A P L 30.000 106 S F C R N K L K Y L
20.000 381 K A I E S L E E G L 17.280 219 K Y T E S P G G G S
12.000 109 R N K L K Y L A F L 8.000 28 K M K Q D K K V D L 8.000
335 H C Q G Q K H N V L 7.200 307 L S P Y G P R N P L 7.200 130 P Y
H F Q V P S R I 7.000 56 H V Q F V G S Y K L 6.600 361 Y V E N G R
P A D L 6.000 157 A S E A Y K K V C L 6.000 377 G A L W K A I E S L
6.000 103 I S G S F C R N K L 5.280 230 R G L G F I F K T I 5.040
160 A Y K K V C L S G A 5.000 66 A Y S N D G E H W T 5.000 278 A A
S P A A W L P L 4.800 12 R A L H I V V E S I 4.200 276 V P A A S P
A A W L 4.000 261 G S S A H R P P A L 4.000 223 S P G G G S P R G L
4.000 193 E I H Y R K N K Q L 4.000 370 L A G S G Y C G A L 4.000 5
T T K T F P L R A L 4.000 227 G S P R G L G F I F 3.600 124 T N P S
R R P Y H F 3.000 92 K A V V V S C E G I 3.000 45 G I I T Q G A K D
F 3.000 50 G A K D F G H V Q F 2.400 7 K T F P L R A L H I 2.400 38
L V P T K V T G I I 2.100 225 G G G S P R G L G F 2.000 37 L L V P
T K V T G I 1.800 208 Q A E K N M K K K I 1.650 94 V V V S C E G I
N I 1.500 204 R L Q K Q A E K N M 1.500 176 K Y Q A V T A T L E
1.500 226 G G S P R G L G F I 1.200 76 V Y Q D E K Q R K D 0.990
320 R H S P S G G G G L 0.960 399 R K A E N G P H L L 0.960 116 A F
L H K R M N T N 0.900 360 W Y V E N G R P A D 0.900 20 S I R D H S
G Q K M 0.792 8 T F P L R A L H I V 0.750 132 H F Q V P S R I F W
0.750 58 Q F V G S Y K L A Y 0.750 29 M K Q D K K V D L L 0.720 80
E K Q R K D K V L L 0.600 53 D F G H V Q F V G S 0.600 309 P Y G P
R N P L P N 0.600 62 S Y K L A Y S N D G 0.600 175 W K Y Q A V T A
T L 0.560 195 H Y R K N K Q L M R 0.500 303 T Y D S L S P Y G P
0.500 235 I F K T I A P L A A 0.500 196 Y R K N K Q L M R L 0.400
398 E R K A E N G P H L 0.400 79 D E K Q R K D K V L 0.400 2 L E H
T T K T F P L 0.400 298 P T S S S T Y D S L 0.400 200 K Q L M R L Q
K Q A 0.360 42 K V T G I I T Q G A 0.336 211 K N M K K K I D K Y
0.330 348 K P Q R K P K S E N 0.330 34 K V D L L V P T K V 0.308
273 R A P V P A A S P A 0.300 400 K A E N G P H L L V 0.300 142 R Q
E K A D G G S C 0.300 313 R N P L P N P R H S 0.300 86 K V L L G R
K A V V 0.300 288 R T P W T R P S S C 0.300 108 C R N K L K Y L A F
0.300 98 C E G I N I S G S F 0.280 30 K Q D K K V D L L V 0.280 346
R G K P Q R K P K S 0.264 16 I V V E S I R D H S 0.252 366 R P A D
L A G S G Y 0.240 168 G A P H E V G W K Y 0.231 293 R P S S C P T S
S S 0.200 131 Y H F Q V P S R I F 0.200 352 K P K S E N N S W Y
0.200 183 T L E E K R K E K A 0.198 67 Y S N D G E H W T V 0.180
274 A P V P A A S P A A 0.180 283 A W L P L R T P W T 0.180 9 F P L
R A L H I V V 0.180 101 I N I S G S F C R N 0.180 151 C C P Q G H A
S E A 0.165 164 V C L S G A P H E V 0.165 87 V L L G R K A V V V
0.150 305 D S L S P Y G P R N 0.150 97 S C E G I N I S G S 0.150 99
E G I N I S G S F C 0.150 152 C P Q G H A S E A Y 0.150 327 G G L K
K P A R H C 0.150 239 I A P L A A T R A T 0.150
[0815]
22TABLE XV Pos 1 2 3 4 5 6 7 8 9 Score Seq ID v.1-B7-9mers: 151P3D4
164 F P R L G R Y N L 1200.000 186 A V I A S F D Q L 60.000 76 K I
R I K W T K L 40.000 159 V V F P Y F P R L 20.000 320 R P R R R C S
P T 20.000 121 D A S L V I T D L 12.000 66 D P T A F G S G I 8.000
106 G G Y Q G R V F L 6.000 148 D T V V V A L D L 4.000 81 W T K L
T S D Y L 4.000 51 S H R G G N V T L 4.000 134 Y G R Y K C E V I
4.000 116 G G S D S D A S L 4.000 224 E P C G G Q N T V 4.000 123 S
L V I T D L T L 4.000 10 I S I C W A D H L 4.000 291 Q I F A A W K
I L 4.000 32 I Q A E N G P H L 4.000 301 Y D R C D A G W L 4.000 33
Q A E N G P H L L 3.600 221 K P R E P C G G Q 3.000 331 A V R F V G
F P D 1.500 180 A C L D Q D A V I 1.200 278 A C L N D G A Q I 1.200
284 A Q I A K V G Q I 1.200 151 V V A L D L Q G V 1.000 313 S V R Y
P I S R P 0.750 207 A G W L S D G S V 0.600 152 V A L D L Q G V V
0.600 179 Q A C L D Q D A V 0.600 306 A G W L A D G S V 0.600 234 G
V R N Y G F W D 0.500 7 L V L I S I C W A 0.500 161 F P Y F P R L G
R 0.450 4 L L L L V L I S I 0.400 22 Y T L D H D R A I 0.400 137 Y
K C E V I E G L 0.400 256 N F N G R F Y Y L 0.400 202 L D W C N A G
W L 0.400 326 S P T E A A V R F 0.400 71 G S G I H K I R I 0.400 16
D H L S D N Y T L 0.400 1 M K S L L L L V L 0.400 290 G Q I F A A W
K I 0.400 336 G F P D K K H K L 0.400 2 K S L L L L V L I 0.400 257
F N G R F Y Y L I 0.400 262 Y Y L I H P T K L 0.400 232 V P G V R N
Y G F 0.400 286 I A K V G Q I F A 0.300 41 L V E A E Q A K V 0.300
122 A S L V I T D L T 0.300 189 A S F D Q L Y D A 0.300 318 I S R P
R R R C S 0.300 197 A W R G G L D W C 0.300 96 V S M G Y H K K T
0.300 324 R C S P T E A A V 0.200 88 Y L K E V D V F V 0.200 217 Y
P I T K P R E P 0.200 316 Y P I S R P R R R 0.200 37 G P H L L V E
A E 0.200 59 L P C K F Y R D P 0.200 245 K S R Y D V F C F 0.200
227 G G Q N T V P G V 0.200 266 H P T K L T Y D E 0.200 84 L T S D
Y L K E V 0.200 143 E G L E D D T V V 0.200 310 A D G S V R Y P I
0.180 194 L Y D A W R G G L 0.180 263 Y L I H P T K L T 0.150 275 A
V Q A C L N D G 0.150 298 I L G Y D R C D A 0.150 346 G V Y C F R A
Y N 0.150 56 N V T L P C K F Y 0.150 48 K V F S H R G G N 0.150 69
A F G S G I H K I 0.120 337 F P D K K H K L Y 0.120 146 E D D T V V
V A L 0.120 174 F H E A Q Q A C L 0.120 272 Y D E A V Q A C L 0.120
249 D V F C F T S N F 0.100 172 L N F H E A Q Q A 0.100 322 R R R C
S P T E A 0.100 90 K E V D V F V S M 0.100 50 F S H R G G N V T
0.100 279 C L N D G A Q I A 0.100 26 H D R A I H I Q A 0.100 167 L
G R Y N L N F H 0.100 5 L L L V L I S I C 0.100 36 N G P H L L V E
A 0.100 270 L T Y D E A V Q A 0.100 178 Q Q A C L D Q D A 0.100 109
Q G R V F L K G G 0.100 199 R G G L D W C N A 0.100 288 K V G Q I F
A A W 0.100 212 D G S V Q Y P I T 0.100 258 N G R F Y Y L I H 0.100
39 H L L V E A E Q A 0.100 276 V Q A C L N D G A 0.100 53 R G G N V
T L P C 0.100 v.2-B7-9mers: 151P3D4 308 S P Y G P R N P L 180.000
81 K Q R K D K V L L 40.000 107 F C R N K L K Y L 40.000 279 A S P
A A W L P L 12.000 378 A L W K A I E S L 12.000 371 A G S G Y C G A
L 12.000 39 V P T K V T G I I 8.000 240 A P L A A T R A T 6.000 104
S G S F C R N K L 6.000 93 A V V V S C E G I 6.000 274 A P V P A A
S P A 6.000 271 S A R A P V P A A 4.500 336 C Q G Q K H N V L 4.000
299 T S S S T Y D S L 4.000 234 F I F K T I A P L 4.000 262 S S A H
R P P A L 4.000 228 S P R G L G F I F 4.000 57 V Q F V G S Y K L
4.000 9 F P L R A L H I V 4.000 321 H S P S G G G G L 4.000 400 K A
E N G P H L L 3.600 382 A I E S L E E G L 3.600 311 G P R N P L P N
P 3.000 38 L V P T K V T G I 2.000 318 N P R H S P S G G 2.000 95 V
V S C E G I N I 2.000 266 R P P A L S A R A 2.000 289 T P W T R P S
S C 2.000 257 T P R A G S S A H 2.000 252 H P G G R T P R A 2.000
152 C P Q G H A S E A 2.000 277 P A A S P A A W L 1.800 86 K V L L
G R K A V 1.500 13 A L H I V V E S I 1.200 169 A P H E V G W K Y
1.200 30 K Q D K K V D L L 1.200 242 L A A T R A T R I 1.200 291 W
T R P S S C P T 1.000 114 Y L A F L H K R M 1.000 205 L Q K Q A E K
N M 1.000 195 H Y R K N K Q L M 1.000 172 E V G W K Y Q A V 1.000 6
T K T F P L R A L 0.600 156 H A S E A Y K K V 0.600 264 A H R P P A
L S A 0.450 254 G G R T P R A G S 0.450 244 A T R A T R I G H 0.450
362 V E N G R P A D L 0.400 29 M K Q D K K V D L 0.400 3 E H T T K
T F P L 0.400 316 L P N P R H S P S 0.400 129 R P Y H F Q V P S
0.400 110 N K L K Y L A F L 0.400 186 E K R K E K A E I 0.400 125 N
P S R R P Y H F 0.400 375 Y C G A L W K A I 0.400 176 K Y Q A V T A
T L 0.400 399 R K A E N G P H L 0.400 227 G S P R G L G F I 0.400
293 R P S S C P T S S 0.400 276 V P A A S P A A W 0.400 352 K P K S
E N N S W 0.400 231 G L G F I F K T I 0.400 80 E K Q R K D K V L
0.400 224 P G G G S P R G L 0.400 314 N P L P N P R H S 0.400 197 R
K N K Q L M R L 0.400 194 I H Y R K N K Q L 0.400 158 S E A Y K K V
C L 0.400 239 I A P L A A T R A 0.300 247 A T R I G H P G G 0.300
344 L A R G K P Q R K 0.300 201 Q L M R L Q K Q A 0.300 370 L A G S
G Y C G A 0.300 297 C P T S S S T Y D 0.200 280 S P A A W L P L R
0.200 285 L P L R T P W T R 0.200 335 H C Q G Q K H N V 0.200 366 R
P A D L A G S G 0.200 49 Q G A K D F G H V 0.200 89 L G R K A V V V
S 0.200 322 S P S G G G G L K 0.200 127 S R R P Y H F Q V 0.200 88
L L G R K A V V V 0.200 135 V P S R I F W R Q 0.200 331 K P A R H C
Q G Q 0.200 10 P L R A L H I V V 0.200 87 V L L G R K A V V 0.200
348 K P Q R K P K S E 0.200 223 S P G G G S P R G 0.200 165 C L S G
A P H E V 0.200 363 E N G R P A D L A 0.150 149 G S C C P Q G H A
0.150 179 A V T A T L E E K 0.150 237 K T I A P L A A T 0.150 249 R
I G H P G G R T 0.150 261 G S S A H R P P A 0.150 36 D L L V P T K
V T 0.150 328 G L K K P A R H C 0.150 282 A A W L P L R T P
0.135
[0816]
23TABLE XVI Pos 1 2 3 4 5 6 7 8 9 0 Score Seq ID v.1-B7-10mers:
151P3D4 158 G V V F P Y F P R L 20.000 185 D A V I A S F D Q L
12.000 122 A S L V I T D L T L 12.000 105 Y G G Y Q G R V F L 6.000
193 Q L Y D A W R G G L 6.000 316 Y P I S R P R R R C 4.500 217 Y P
I T K P R E P C 4.500 335 V G F P D K K H K L 4.000 9 L I S I C W A
D H L 4.000 255 S N F N G R F Y Y L 4.000 32 I Q A E N G P H L L
4.000 221 K P R E P C G G Q N 4.000 50 F S H R G G N V T L 4.000
290 G Q I F A A W K I L 4.000 115 K G G S D S D A S L 4.000 164 F P
R L G R Y N L N 4.000 31 H I Q A E N G P H L 4.000 326 S P T E A A
V R F V 4.000 59 L P C K F Y R D P T 3.000 320 R P R R R C S P T E
2.000 266 H P T K L T Y D E A 2.000 331 A V R F V G F P D K 1.500
275 A V Q A C L N D G A 1.500 179 Q A C L D Q D A V I 1.200 15 A D
H L S D N Y T L 1.200 277 Q A C L N D G A Q I 1.200 283 G A Q I A K
V G Q I 1.200 201 G L D W C N A G W L 1.200 68 T A F G S G I H K I
1.200 48 K V F S H R G G N V 1.000 151 V V A L D L Q G V V 1.000
150 V V V A L D L Q G V 1.000 245 K S R Y D V F C F T 1.000 76 K I
R I K W T K L T 1.000 305 D A G W L A D G S V 0.600 206 N A G W L S
D G S V 0.600 163 Y F P R L G R Y N L 0.600 309 L A D G S V R Y P I
0.540 234 G V R N Y G F W D K 0.500 140 E V I E G L E D D T 0.500
95 F V S M G Y H K K T 0.500 313 S V R Y P I S R P R 0.500 70 F G S
G I H K I R I 0.400 161 F P Y F P R L G R Y 0.400 136 R Y K C E V I
E G L 0.400 147 D D T V V V A L D L 0.400 173 N F H E A Q Q A C L
0.400 232 V P G V R N Y G F W 0.400 289 V G Q I F A A W K I 0.400
75 H K I R I K W T K L 0.400 261 F Y Y L I H P T K L 0.400 3 S L L
L L V L I S I 0.400 120 S D A S L V I T D L 0.400 80 K W T K L T S
D Y L 0.400 286 I A K V G Q I F A A 0.300 121 D A S L V I T D L T
0.300 186 A V I A S F D Q L Y 0.300 188 I A S F D Q L Y D A 0.300
180 A C L D Q D A V I A 0.300 196 D A W R G G L D W C 0.300 177 A Q
Q A C L D Q D A 0.300 278 A C L N D G A Q I A 0.300 33 Q A E N G P
H L L V 0.270 66 D P T A F G S G I H 0.200 226 C G G Q N T V P G V
0.200 224 E P C G G Q N T V P 0.200 116 G G S D S D A S L V 0.200
109 Q G R V F L K G G S 0.200 37 G P H L L V E A E Q 0.200 178 Q Q
A C L D Q D A V 0.200 143 E G L E D D T V V V 0.200 103 K T Y G G Y
Q G R V 0.200 40 L L V E A E Q A K V 0.200 83 K L T S D Y L K E V
0.200 297 K I L G Y D R C D A 0.150 318 I S R P R R R C S P 0.150
322 R R R C S P T E A A 0.150 271 T Y D E A V Q A C L 0.120 145 L E
D D T V V V A L 0.120 117 G S D S D A S L V I 0.120 210 L S D G S V
Q Y P I 0.120 300 G Y D R C D A G W L 0.120 23 T L D H D R A I H I
0.120 167 L G R Y N L N F H E 0.100 249 D V F C F T S N F N 0.100
269 K L T Y D E A V Q A 0.100 73 G I H K I R I K W T 0.100 6 L L V
L I S I C W A 0.100 35 E N G P H L L V E A 0.100 20 D N Y T L D H D
R A 0.100 270 L T Y D E A V Q A C 0.100 285 Q I A K V G Q I F A
0.100 111 R V F L K G G S D S 0.100 172 L N F H E A Q Q A C 0.100
171 N L N F H E A Q Q A 0.100 134 Y G R Y K C E V I E 0.100 113 F L
K G G S D S D A 0.100 343 K L Y G V Y C F R A 0.100 4 L L L L V L I
S I C 0.100 231 T V P G V R N Y G F 0.100 v.2-B7-10mers: 151P3D4
276 V P A A S P A A W L 120.000 223 S P G G G S P R G L 80.000 278
A A S P A A W L P L 36.000 56 H V Q F V G S Y K L 20.000 377 G A L
W K A I E S L 12.000 370 L A G S G Y C G A L 12.000 381 K A I E S L
E E G L 12.000 20 S I R D H S G Q K M 10.000 307 L S P Y G P R N P
L 9.000 5 T T K T F P L R A L 6.000 361 Y V E N G R P A D L 6.000
103 I S G S F C R N K L 6.000 274 A P V P A A S P A A 6.000 109 R N
K L K Y L A F L 4.000 335 H C Q G Q K H N V L 4.000 261 G S S A H R
P P A L 4.000 28 K M K Q D K K V D L 4.000 9 F P L R A L H I V V
4.000 193 E I H Y R K N K Q L 4.000 157 A S E A Y K K V C L 3.600
318 N P R H S P S G G G 3.000 39 V P T K V T G I I T 2.000 94 V V V
S C E G I N I 2.000 228 S P R G L G F I F K 2.000 311 G P R N P L P
N P R 2.000 38 L V P T K V T G I I 2.000 257 T P R A G S S A H R
2.000 280 S P A A W L P L R T 2.000 92 K A V V V S C E G I 1.200 12
R A L H I V V E S I 1.200 89 L G R K A V V V S C 1.000 107 F C R N
K L K Y L A 1.000 204 R L Q K Q A E K N M 1.000 86 K V L L G R K A
V V 1.000 240 A P L A A T R A T R 0.900 169 A P H E V G W K Y Q
0.600 348 K P Q R K P K S E N 0.600 267 P P A L S A R A P V 0.600
293 R P S S C P T S S S 0.600 271 S A R A P V P A A S 0.600 42 K V
T G I I T Q G A 0.500 172 E V G W K Y Q A V T 0.500 115 L A F L H K
R M N T 0.450 260 A G S S A H R P P A 0.450 263 S A H R P P A L S A
0.450 344 L A R G K P Q R K P 0.450 314 N P L P N P R H S P 0.450
226 G G S P R G L G F I 0.400 106 S F C R N K L K Y L 0.400 398 E R
K A E N G P H L 0.400 366 R P A D L A G S G Y 0.400 2 L E H T T K T
F P L 0.400 175 W K Y Q A V T A T L 0.400 152 C P Q G H A S E A Y
0.400 79 D E K Q R K D K V L 0.400 399 R K A E N G P H L L 0.400
320 R H S P S G G G G L 0.400 297 C P T S S S T Y D S 0.400 298 P T
S S S T Y D S L 0.400 233 G F I F K T I A P L 0.400 196 Y R K N K Q
L M R L 0.400 230 R G L G F I F K T I 0.400 7 K T F P L R A L H I
0.400 80 E K Q R K D K V L L 0.400 352 K P K S E N N S W Y 0.400 29
M K Q D K K V D L L 0.400 37 L L V P T K V T G I 0.400 208 Q A E K
N M K K K I 0.360 239 I A P L A A T R A T 0.300 34 K V D L L V P T
K V 0.300 289 T P W T R P S S C P 0.300 125 N P S R R P Y H F Q
0.300 156 H A S E A Y K K V C 0.300 247 A T R I G H P G G R 0.300
244 A T R A T R I G H P 0.300 269 A L S A R A P V P A 0.300 285 L P
L R T P W T R P 0.300 93 A V V V S C E G I N 0.300 273 R A P V P A
A S P A 0.300 282 A A W L P L R T P W 0.270 400 K A E N G P H L L V
0.270 291 W T R P S S C P T S 0.200 26 G Q K M K Q D K K V 0.200
164 V C L S G A P H E V 0.200 252 H P G G R T P R A G 0.200 322 S P
S G G G G L K K 0.200 308 S P Y G P R N P L P 0.200 87 V L L G R K
A V V V 0.200 67 Y S N D G E H W T V 0.200 129 R P Y H F Q V P S R
0.200 331 K P A R H C Q G Q K 0.200 254 G G R T P R A G S S 0.200
126 P S R R P Y H F Q V 0.200 364 N G R P A D L A G S 0.200 266 R P
P A L S A R A P 0.200 48 T Q G A K D F G H V 0.200 316 L P N P R H
S P S G 0.200 135 V P S R I F W R Q E 0.200 179 A V T A T L E E K R
0.150 327 G G L K K P A R H C 0.150
[0817]
24TABLE XVII Pos 1 2 3 4 5 6 7 8 9 Score Seq ID v.1-B35-9mers:
151P3D4 164 F P R L G R Y N L 60.000 245 K S R Y D V F C F 45.000
326 S P T E A A V R F 40.000 232 V P G V R N Y G F 20.000 320 R P R
R R C S P T 12.000 337 F P D K K H K L Y 12.000 254 T S N F N G R F
Y 10.000 66 D P T A F G S G I 8.000 76 K I R I K W T K L 6.000 293
F A A W K I L G Y 6.000 129 L T L E D Y G R Y 6.000 10 I S I C W A
D H L 5.000 209 W L S D G S V Q Y 4.000 308 W L A D G S V R Y 4.000
224 E P C G G Q N T V 4.000 2 K S L L L L V L I 4.000 81 W T K L T
S D Y L 3.000 121 D A S L V I T D L 3.000 329 E A A V R F V G F
3.000 221 K P R E P C G G Q 2.400 187 V I A S F D Q L Y 2.000 230 N
T V P G V R N Y 2.000 255 S N F N G R F Y Y 2.000 71 G S G I H K I
R I 2.000 345 Y G V Y C F R A Y 2.000 166 R L G R Y N L N F 2.000
116 G G S D S D A S L 2.000 264 L I H P T K L T Y 2.000 97 S M G Y
H K K T Y 2.000 56 N V T L P C K F Y 2.000 155 D L Q G V V F P Y
2.000 32 I Q A E N G P H L 2.000 14 W A D H L S D N Y 1.800 196 D A
W R G G L D W 1.500 318 I S R P R R R C S 1.500 134 Y G R Y K C E V
I 1.200 88 Y L K E V D V F V 1.200 152 V A L D L Q G V V 1.200 106
G G Y Q G R V F L 1.000 148 D T V V V A L D L 1.000 189 A S F D Q L
Y D A 1.000 186 A V I A S F D Q L 1.000 253 F T S N F N G R F 1.000
123 S L V I T D L T L 1.000 55 G N V T L P C K F 1.000 159 V V F P
Y F P R L 1.000 285 Q I A K V G Q I F 1.000 156 L Q G V V F P Y F
1.000 249 D V F C F T S N F 1.000 291 Q I F A A W K I L 1.000 105 Y
G G Y Q G R V F 1.000 288 K V G Q I F A A W 1.000 179 Q A C L D Q D
A V 0.900 286 I A K V G Q I F A 0.900 33 Q A E N G P H L L 0.900 90
K E V D V F V S M 0.800 22 Y T L D H D R A I 0.800 180 A C L D Q D
A V I 0.800 278 A C L N D G A Q I 0.600 243 K D K S R Y D V F 0.600
100 Y H K K T Y G G Y 0.600 78 R I K W T K L T S 0.600 143 E G L E
D D T V V 0.600 28 R A I H I Q A E N 0.600 126 I T D L T L E D Y
0.600 96 V S M G Y H K K T 0.500 122 A S L V I T D L T 0.500 6 L L
V L I S I C W 0.500 50 F S H R G G N V T 0.500 73 G I H K I R I K W
0.500 301 Y D R C D A G W L 0.450 117 G S D S D A S L V 0.450 84 L
T S D Y L K E V 0.400 80 K W T K L T S D Y 0.400 284 A Q I A K V G
Q I 0.400 324 R C S P T E A A V 0.400 257 F N G R F Y Y L I 0.400 4
L L L L V L I S I 0.400 290 G Q I F A A W K I 0.400 340 K K H K L Y
G V Y 0.400 153 A L D L Q G V V F 0.300 305 D A G W L A D G S 0.300
199 R G G L D W C N A 0.300 115 K G G S D S D A S 0.300 151 V V A L
D L Q G V 0.300 51 S H R G G N V T L 0.300 206 N A G W L S D G S
0.300 62 K F Y R D P T A F 0.300 183 D Q D A V I A S F 0.300 270 L
T Y D E A V Q A 0.300 42 V E A E Q A K V F 0.200 53 R G G N V T L P
C 0.200 59 L P C K F Y R D P 0.200 306 A G W L A D G S V 0.200 137
Y K C E V I E G L 0.200 227 G G Q N T V P G V 0.200 37 G P H L L V
E A E 0.200 161 F P Y F P R L G R 0.200 336 G F P D K K H K L 0.200
48 K V F S H R G G N 0.200 v.2-B35-9mers: 151P3D4 352 K P K S E N N
S w 90.000 169 A P H E V G W K Y 80.000 228 S P R G L G F I F
60.000 308 S P Y G P R N P L 20.000 125 N P S R R P Y H F 20.000
276 V P A A S P A A W 10.000 81 K Q R K D K V L L 9.000 39 V P T K
V T G I I 8.000 205 L Q K Q A E K N M 6.000 212 N M K K K I D K Y
6.000 109 R N K L K Y L A F 6.000 299 T S S S T Y D S L 5.000 262 S
S A H R P P A L 5.000 321 H S P S G G G G L 5.000 279 A S P A A W L
P L 5.000 302 S T Y D S L S P Y 4.000 129 R P Y H F Q V P S 4.000
266 R P P A L S A R A 4.000 9 F P L R A L H I V 4.000 293 R P S S C
P T S S 4.000 107 F C R N K L K Y L 3.000 372 G S G Y C G A L W
2.500 316 L P N P R H S P S 2.000 274 A P V P A A S P A 2.000 152 C
P Q G H A S E A 2.000 252 H P G G R T P R A 2.000 296 S C P T S S S
T Y 2.000 240 A P L A A T R A T 2.000 114 Y L A F L H K R M 2.000
227 G S P R G L G F I 2.000 123 N T N P S R R P Y 2.000 59 F V G S
Y K L A Y 2.000 289 T P W T R P S S C 2.000 314 N P L P N P R H S
2.000 400 K A E N G P H L L 1.800 242 L A A T R A T R I 1.200 393 K
Q K D K E R K A 1.200 156 H A S E A Y K K V 1.200 371 A G S G Y C G
A L 1.000 99 E G I N I S G S F 1.000 336 C Q G Q K H N V L 1.000
104 S G S F C R N K L 1.000 234 F I F K T I A P L 1.000 378 A L W K
A I E S L 1.000 57 V Q F V G S Y K L 1.000 46 I I T Q G A K D F
1.000 226 G G S P R G L G F 1.000 96 V S C E G I N I S 1.000 67 Y S
N D G E H W T 1.000 271 S A R A P V P A A 0.900 366 R P A D L A G S
G 0.800 257 T P R A G S S A H 0.600 318 N P R H S P S G G 0.600 195
H Y R K N K Q L M 0.600 95 V V S C E G I N I 0.600 12 R A L H I V V
E S 0.600 354 K S E N N S W Y V 0.600 311 G P R N P L P N P 0.600
30 K Q D K K V D L L 0.600 261 G S S A H R P P A 0.500 300 S S S T
Y D S L S 0.500 270 L S A R A P V P A 0.500 167 S G A P H E V G W
0.500 295 S S C P T S S S T 0.500 149 G S C C P Q G H A 0.500 61 G
S Y K L A Y S N 0.500 133 F Q V P S R I F W 0.500 69 N D G E H W T
V Y 0.400 13 A L H I V V E S I 0.400 231 G L G F I F K T I 0.400 38
L V P T K V T G I 0.400 375 Y C G A L W K A I 0.400 348 K P Q R K P
K S E 0.400 86 K V L L G R K A V 0.400 93 A V V V S C E G I 0.400
399 R K A E N G P H L 0.400 331 K P A R H C Q G Q 0.400 328 G L K K
P A R H C 0.300 277 P A A S P A A W L 0.300 239 I A P L A A T R A
0.300 89 L G R K A V V V S 0.300 49 Q G A K D F G H V 0.300 382 A I
E S L E E G L 0.300 254 G G R T P R A G S 0.300 291 W T R P S S C P
T 0.300 377 G A L W K A I E S 0.300 263 S A H R P P A L S 0.300 159
E A Y K K V C L S 0.300 1 M L E H T T K T F 0.300 370 L A G S G Y C
G A 0.300 115 L A F L H K R M N 0.300 5 T T K T F P L R A 0.300 230
R G L G F I F K T 0.200 280 S P A A W L P L R 0.200 138 R I F W R Q
E K A 0.200 322 S P S G G G G L K 0.200 288 R T P W T R P S S 0.200
297 C P T S S S T Y D 0.200 249 R I G H P G G R T 0.200 204 R L Q K
Q A E K N 0.200
[0818]
25TABLE XVIII Pos 1 2 3 4 5 6 7 8 9 0 Score Seq ID v.1-B35-10mers:
151P3D4 161 F P Y F P R L G R Y 40.000 221 K P R E P C G G Q N
24.000 254 T S N F N G R F Y Y 10.000 96 V S M G Y H K K T Y 10.000
232 V P G V R N Y G F W 10.000 326 S P T E A A V R F V 8.000 164 F
P R L G R Y N L N 6.000 152 V A L D L Q G V V F 6.000 122 A S L V I
T D L T L 5.000 325 C S P T E A A V R F 5.000 189 A S F D Q L Y D A
W 5.000 50 F S H R G G N V T L 5.000 125 V I T D L T L E D Y 4.000
185 D A V I A S F D Q L 3.000 128 D L T L E D Y G R Y 3.000 245 K S
R Y D V F C F T 3.000 55 G N V T L P C K F Y 2.000 115 K G G S D S
D A S L 2.000 59 L P C K F Y R D P T 2.000 217 Y P I T K P R E P C
2.000 229 Q N T V P G V R N Y 2.000 253 F T S N F N G R F Y 2.000
32 I Q A E N G P H L L 2.000 193 Q L Y D A W R G G L 2.000 263 Y L
I H P T K L T Y 2.000 186 A V I A S F D Q L Y 2.000 316 Y P I S R P
R R R C 2.000 266 H P T K L T Y D E A 2.000 277 Q A C L N D G A Q I
1.800 68 T A F G S G I H K I 1.200 179 Q A C L D Q D A V I 1.200
283 G A Q I A K V G Q I 1.200 320 R P R R R C S P T E 1.200 284 A Q
I A K V G Q I F 1.000 335 V G F P D K K H K L 1.000 299 L G Y D R C
D A G W 1.000 105 Y G G Y Q G R V F L 1.000 290 G Q I F A A W K I L
1.000 255 S N F N G R F Y Y L 1.000 158 G V V F P Y F P R L 1.000
231 T V P G V R N Y G F 1.000 2 K S L L L L V L I S 1.000 200 G G L
D W C N A G W 1.000 31 H I Q A E N G P H L 1.000 54 G G N V T L P C
K F 1.000 9 L I S I C W A D H L 1.000 155 D L Q G V V F P Y F 1.000
88 Y L K E V D V F V S 0.900 286 I A K V G Q I F A A 0.900 91 E V D
V F V S M G Y 0.600 210 L S D G S V Q Y P I 0.600 305 D A G W L A D
G S V 0.600 136 R Y K C E V I E G L 0.600 206 N A G W L S D G S V
0.600 117 G S D S D A S L V I 0.600 339 D K K H K L Y G V Y 0.600
143 E G L E D D T V V V 0.600 116 G G S D S D A S L V 0.600 239 G F
W D K D K S R Y 0.600 76 K I R I K W T K L T 0.600 341 K H K L Y G
V Y C F 0.600 40 L L V E A E Q A K V 0.600 10 I S I C W A D H L S
0.500 5 L L L V L I S I C W 0.500 72 S G I H K I R I K W 0.500 103
K T Y G G Y Q G R V 0.400 336 G F P D K K H K L Y 0.400 13 C W A D
H L S D N Y 0.400 48 K V F S H R G G N V 0.400 3 S L L L L V L I S
I 0.400 289 V G Q I F A A W K I 0.400 70 F G S G I H K I R I 0.400
83 K L T S D Y L K E V 0.400 309 L A D G S V R Y P I 0.360 297 K I
L G Y D R C D A 0.300 109 Q G R V F L K G G S 0.300 269 K L T Y D E
A V Q A 0.300 180 A C L D Q D A V I A 0.300 201 G L D W C N A G W L
0.300 121 D A S L V I T D L T 0.300 41 L V E A E Q A K V F 0.300
196 D A W R G G L D W C 0.300 188 I A S F D Q L Y D A 0.300 150 V V
V A L D L Q G V 0.300 178 Q Q A C L D Q D A V 0.300 113 F L K G G S
D S D A 0.300 85 T S D Y L K E V D V 0.300 111 R V F L K G G S D S
0.200 151 V V A L D L Q G V V 0.200 344 L Y G V Y C F R A Y 0.200
343 K L Y G V Y C F R A 0.200 307 G W L A D G S V R Y 0.200 292 I F
A A W K I L G Y 0.200 80 K W T K L T S D Y L 0.200 182 L D Q D A V
I A S F 0.200 66 D P T A F G S G I H 0.200 270 L T Y D E A V Q A C
0.200 99 G Y H K K T Y G G Y 0.200 226 C G G Q N T V P G V 0.200
224 E P C G G Q N T V P 0.200 v.2-B35-10mers: 151P3D4 352 K P K S E
N N S W Y 240.000 366 R P A D L A G S G Y 160.000 152 C P Q G H A S
E A Y 40.000 276 V P A A S P A A W L 20.000 223 S P G G G S P R G L
20.000 50 G A K D F G H V Q F 18.000 20 S I R D H S G Q K M 12.000
381 K A I E S L E E G L 12.000 301 S S T Y D S L S P Y 10.000 105 G
S F C R N K L K Y 10.000 295 S S C P T S S S T Y 10.000 109 R N K L
K Y L A F L 6.000 168 G A P H E V G W K Y 6.000 28 K M K Q D K K V
D L 6.000 227 G S P R G L G F I F 5.000 261 G S S A H R P P A L
5.000 307 L S P Y G P R N P L 5.000 103 I S G S F C R N K L 5.000
348 K P Q R K P K S E N 4.000 9 F P L R A L H I V V 4.000 211 K N M
K K K I D K Y 4.000 293 R P S S C P T S S S 4.000 204 R L Q K Q A E
K N M 4.000 67 Y S N D G E H W T V 3.000 370 L A G S G Y C G A L
3.000 278 A A S P A A W L P L 3.000 377 G A L W K A I E S L 3.000 5
T T K T F P L R A L 3.000 166 L S G A F H E V G W 2.500 187 K R K E
K A E I H Y 2.400 12 R A L H I V V E S I 2.400 92 K A V V V S C E G
I 2.400 65 L A Y S N D G E H W 2.250 39 V P T K V T G I I T 2.000
297 C P T S S S T Y D S 2.000 280 S P A A W L P L R T 2.000 274 A P
V P A A S P A A 2.000 54 F G H V Q F V G S Y 2.000 122 M N T N P S
R R P Y 2.000 282 A A W L P L R T P W 1.500 157 A S E A Y K K V C L
1.500 56 H V Q F V G S Y K L 1.000 193 E I H Y R K N K Q L 1.000 45
G I I T Q G A K D F 1.000 225 G G G S P R G L G F 1.000 335 H C Q G
Q K H N V L 1.000 124 T N P S R R P Y H F 1.000 271 S A R A P V P A
A S 0.900 7 K T F P L R A L H I 0.800 230 R G L G F I F K T I 0.800
68 S N D G E H W T V Y 0.600 311 G P R N P L P N P R 0.600 94 V V V
S C E G I N I 0.600 273 R A P V P A A S P A 0.600 228 S P R G L G F
I F K 0.600 156 H A S E A Y K K V C 0.600 257 T P R A G S S A H R
0.600 346 R G K P Q R K P K S 0.600 26 G Q K M K Q D K K V 0.600
318 N P R H S P S G G G 0.600 371 A G S G Y C G A L W 0.500 299 T S
S S T Y D S L S 0.500 149 G S C C P Q G H A S 0.500 305 D S L S P Y
G P R N 0.500 270 L S A R A P V P A A 0.500 262 S S A H R P P A L S
0.500 364 N G R P A D L A G S 0.450 86 K V L L G R K A V V 0.400
399 R K A E N G P H L L 0.400 226 G G S P R G L G F I 0.400 266 R P
P A L S A R A P 0.400 37 L L V P T K V T G I 0.400 129 R P Y H F Q
V P S R 0.400 113 K Y L A F L H K R M 0.400 169 A P H E V G W K Y Q
0.400 38 L V P T K V T G I I 0.400 267 P P A L S A R A P V 0.400
331 K P A R H C Q G Q K 0.400 208 Q A E K N M K K K I 0.360 400 K A
E N G P H L L V 0.360 79 D E K Q R K D K V L 0.300 107 F C R N K L
K Y L A 0.300 115 L A F L H K R M N T 0.300 398 E R K A E N G P H L
0.300 239 I A P L A A T R A T 0.300 361 Y V E N G R P A D L 0.300
291 W T R P S S C P T S 0.300 263 S A H R P P A L S A 0.300 212 N M
K K K I D K Y T 0.300 196 Y R K N K Q L M R L 0.300 254 G G R T P R
A G S S 0.300 126 P S R R P Y H F Q V 0.300 89 L G R K A V V V S C
0.300 48 T Q G A K D F G H V 0.300 314 N P L P N P R H S P 0.200
194 I H Y R K N K Q L M 0.200 322 S P S G G G G L K K 0.200 164 V C
L S G A P H E V 0.200 288 R T P W T R P S S C 0.200 42 K V T G I I
T Q G A 0.200
[0819]
26TABLE XIX Frequently Occurring Motifs avrg. % Name identity
Description Potential Function zf-C2H2 34% Zinc finger, C2H2 type
Nucleic acid-binding protein functions as transcription factor,
nuclear location probable cytochrome_b_N 68% Cytochrome b(N-
membrane bound oxidase, generate terminal)/b6/petB superoxide ig
19% Immunoglobulin domain domains are one hundred amino acids long
and include a conserved intradomain disulfide bond. WD40 18% WD
domain, G-beta tandem repeats of about 40 repeat residues, each
containing a Trp-Asp motif. Function in signal transduction and
protein interaction PDZ 23% PDZ domain may function in targeting
signaling molecules to sub-membranous sites LRR 28% Leucine Rich
Repeat short sequence motifs involved in protein-protein
interactions pkinase 23% Protein kinase domain conserved catalytic
core common to both serine/threonine and tyrosine protein kinases
containing an ATP binding site and a catalytic site PH 16% PH
domain pleckstrin homology involved in intracellular signaling or
as constituents of the cytoskeleton EGF 34% EGF-like domain 30-40
amino-acid long found in the extracellular domain of membrane-
bound proteins or in secreted proteins rvt 49% Reverse
transcriptase (RNA-dependent DNA polymerase) ank 25% Ank repeat
Cytoplasmic protein, associates integral membrane proteins to the
cytoskeleton oxidored_q1 32% NADH- membrane associated. Involved in
Ubiquinone/plastoquinone proton translocation across the (complex
I), various membrane chains efhand 24% EF hand calcium-binding
domain, consists of a12 residue loop flanked on both sides by a 12
residue alpha-helical domain rvp 79% Retroviral aspartyl Aspartyl
or acid proteases, centered protease on a catalytic aspartyl
residue Collagen 42% Collagen triple helix extracellular structural
proteins repeat (20 copies) involved in formation of connective
tissue. The sequence consists of the G-X-Y and the polypeptide
chains forms a triple helix. fn3 20% Fibronectin type III Located
in the extracellular ligand- domain binding region of receptors and
is about 200 amino acid residues long with two pairs of cysteines
involved in disulfide bonds 7tm_1 19% 7 transmembrane seven
hydrophobic transmembrane receptor (rhodopsin regions, with the
N-terminus family) located extracellularly while the C- terminus is
cytoplasmic. Signal through G proteins
[0820]
27TABLE XX Motifs and Post-translational Modifications of 151P3D4
N-glycosylation site. 21-24 NYTL 56-59 NVTL cAMP- and
cGMP-dependent protein kinase phosphorylation site 323-326 RRcS
Protein kinase C phosphorylation site 51-53 ShR 313-315 SvR Casein
kinase II phosphorylation site 118-121 SdsD 130-133 TleD 246-249
SryD 271-274 TydE 326-329 SptE N-myristoylation site 54-59 GGnvTL
106-111 GGyqGR 116-121 GGsdSD 201-206 GLdwCN 227-232 GGqnTV 283-288
GAqiAK 290-295 GQifAA
[0821]
28TABLE XXI Protein Properties of 151P3D4 Bioinformatic Program URL
Outcome 151P3D4 V.1 ORF ORF finder bp316-1380 (includes stop)
Protein length 354 aa Transmembrane TM Pred
http://www.ch.embnet.org/ no TM region HMMTop
http://www.enzim.hu/hmmtop/ no TM, intracellular Sosui
http://www.genome.ad.jp/SOSui/ no TM, soluble protein TMHMM
http://www.cbs.dtu.dk/services/TMHMM no TM Signal Peptide Signal P
http://www.cbs.dtu.dk/services/SignalP/ yes pI pI/MW tool
http://www.expasy.ch/tools/ 7.1 Molecular weight pI/MW tool
http://www.expasy.ch/tools/ 40.1 kDa Localization PSORT
http://psort.nibb.ac.jp/ 53% outside, 51% lysosome PSORT II
http://psort.nibb.ac.jp/ 66% extracellular, 11% cytoplasmic Motifs
Pfam http://www.sanger.ac.uk/Pfam/ Ig domain, extracellular link
domain Prints http://www.biochem.ucl.ac.uk/ Link module Blocks
http://www.blocks.fhcrc.org/ Link motif, C-type lectin domain,
receptor tyrosine kinase class III 151P3D4 V.2 ORF ORF finder
bp1-2166 (includes stop) Protein length 721 aa Transmembrane TM
Pred http://www.ch.embnet.org/ no TM region HMMTop
http://www.enzim.hu/hmmtop/ no TM, extracellular Sosui
http://www.genome.ad.jp/SOSui/ no TM, soluble protein TMHMM
http://www.cbs.dtu.dk/services/TMHMM no TM Signal Peptide Signal P
http://www.cbs.dtu.dk/services/SignalP/ none pI pI/MW tool
http://www.expasy.ch/tools/ pI9.6 Molecular weight pI/MW tool
http://www.expasy.ch/tools/ 80.7 kDa Localization PSORT
http://psort.nibb.ac.jp/ 82% nucleus, 42% peroxisome PSORT II
http://psort.nibb.ac.jp/ 52% nuclear, 26% cytoplasmic Motifs Pfam
http://www.sanger.ac.uk/Pfam/ F5/8 type C domain, Ig domain
extracellular link domain Prints http://www.biochem.ucl.ac.uk/ link
module signature Blocks http://www.blocks.fhcrc.org/ Link motif,
coagulation factor 5/8 type c domain (FA58C), ribosomal protein
L13, C-type lectin domain, receptor tyrosine kinase class III
[0822]
29TABLE XXII SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:
HLA Peptide Scoring Results A1 9-mers SYFPEITHI 126 I T D L T L E D
Y 31 230 N T V P G V R N Y 28 337 F P D K K H K L Y 28 240 F W D K
D K S R Y 26 14 W A D H L S D N Y 25 264 L I H P T K L T Y 25 293 F
A A W K I L G Y 22 18 L S D N Y T L D H 21 129 L T L E D Y G R Y 21
155 D L Q G V V F P Y 20 254 T S N F N G R F Y 20 255 S N F N G R F
Y Y 20 345 Y G V Y C F R A Y 20 162 P Y F P R L G R Y 19 92 V D V F
V S M G Y 18 187 V I A S F D Q L Y 18 209 W L S D G S V Q Y 18 303
R C D A G W L A D 18 308 W L A D G S V R Y 18 97 S M G Y H K K T Y
17 100 Y H K K T Y G G Y 17 327 P T E A A V R F V 17 56 N V T L P C
K F Y 16 64 Y R D P T A F G S 16 117 G S D S D A S L V 16 153 A L D
L Q G V V F 16 210 L S D G S V Q Y P 16 340 K K H K L Y G V Y 16 80
K W T K L T S D Y 15 85 T S D Y L K E V D 15 108 Y Q G R V F L K G
15 131 L E D Y G R Y K C 15 222 P R E P C G G Q N 15 280 L N D G A
Q I A K 15 33 Q A E N G P H L L 14 119 D S D A S L V I T 14 148 D T
V V V A L D L 14 272 Y D E A V Q A C L 14 130 T L E D Y G R Y K 13
146 E D D T V V V A L 13 174 F H E A Q Q A C L 13 23 T L D H D R A
I H 12 41 L V E A E Q A K V 12 89 L K E V D V F V S 12 91 E V D V F
V S M G 12 138 K C E V I E G L E 12 141 V I E G L E D D T 12 144 G
L E D D T V V V 12 145 L E D D T V V V A 12 183 D Q D A V I A S F
12 190 S F D Q L Y D A W 12 201 G L D W C N A G W 12 309 L A D G S
V R Y P 12 34 A E N G P H L L V 11 35 E N G P H L L V E 11 57 V T L
P C K F Y R 11 181 C L D Q D A V I A 11 194 L Y D A W R G G L 11
242 D K D K S R Y D V 11 271 T Y D E A V Q A C 11 3 S L L L L V L I
S 10 25 D H D R A I H I Q 10 43 E A E Q A K V F S 10 219 I T K P R
E P C G 10 247 R Y D V F C F T S 10 300 G Y D R C D A G W 10 50 F S
H R G G N V T 9 83 K L T S D Y L K E 9 96 V S M G Y H K K T 9 103 K
T Y G G Y Q G R 9 118 S D S D A S L V I 9 123 S L V I T D L T L 9
159 V V F P Y F P R L 9 161 F P Y F P R L G R 9 166 R L G R Y N L N
F 9 196 D A W R G G L D W 9 213 G S V Q Y P I T K 9 312 G S V R Y P
I S R 9 318 I S R P R R R C S 9 22 Y T L D H D R A I 8 53 R G G N V
T L P C 8 67 P T A F G S G I H 8 71 G S G I H K I R I 8 204 W C N A
G W L S D 8 253 F T S N F N G R F 8 1 M K S L L L L V L 7 4 L L L L
V L I S I 7 73 G I H K I R I K W 7 84 L T S D Y L K E V 7 120 S D A
S L V I T D 7 122 A S L V I T D L T 7 125 V I T D L T L E D 7 139 C
E V I E G L E D 7 150 V V V A L D L Q G 7 189 A S F D Q L Y D A 7
246 S R Y D V F C F T 7 258 N G R F Y Y L I H 7 2 K S L L L L V L I
6 12 I C W A D H L S D 6 51 S H R G G N V T L 6 68 T A F G S G I H
K 6 78 R I K W T K L T S 6 81 W T K L T S D Y L 6 105 Y G G Y Q G R
V F 6 176 E A Q Q A C L D Q 6 188 I A S F D Q L Y D 6 235 V R N Y G
F W D K 6 263 Y L I H P T K L T 6 267 P T K L T Y D E A 6 270 L T Y
D E A V Q A 6 274 E A V Q A C L N D 6 286 I A K V G Q I F A 6 292 I
F A A W K I L G 6 332 V R F V G F P D K 6 338 P D K K H K L Y G 6 6
L L V L I S I C W 5 45 E Q A K V F S H R 5 69 A F G S G I H K I 5
88 Y L K E V D V F V 5 90 K E V D V F V S M 5 95 F V S M G Y H K K
5 113 F L K G G S D S D 5 136 R Y K C E V I E G 5 147 D D T V V V A
L D 5 156 L Q G V V F P Y F 5 182 L D Q D A V I A S 5 195 Y D A W R
G G L D 5 214 S V Q Y P I T K P 5 215 V Q Y P I T K P R 5 225 P C G
G Q N T V P 5 245 K S R Y D V F C F 5 248 Y D V F C F T S N 5 259 G
R F Y Y L I H P 5 314 V R Y P I S R P R 5 325 C S P T E A A V R 5
335 V G F P D K K H K 5 10 I S I C W A D H L 4 11 S I C W A D H L S
4 24 L D H D R A I H I 4 26 H D R A I H I Q A 4 42 V E A E Q A K V
F 4 52 H R G G N V T L P 4 58 T L P C K F Y R D 4 107 G Y Q G R V F
L K 4 112 V F L K G G S D S 4 137 Y K C E V I E G L 4 164 F P R L G
R Y N L 4 175 H E A Q Q A C L D 4 180 A C L D Q D A V I 4 186 A V I
A S F D Q L 4 197 A W R G G L D W C 4 211 S D G S V Q Y P I 4 231 T
V P G V R N Y G 4 238 Y G F W D K D K S 4 256 N F N G R F Y Y L 4
262 Y Y L I H P T K L 4 273 D E A V Q A C L N 4 281 N D G A Q I A K
V 4 287 A K V G Q I F A A 4 310 A D G S V R Y P I 4 324 R C S P T E
A A V 4 328 T E A A V R F V G 4 331 A V R F V G F P D 4 334 F V G F
P D K K H 4 343 K L Y G V Y C F R 4 17 H L S D N Y T L D 3 29 A I H
I Q A E N G 3 65 R D P T A F G S G 3 102 K K T Y G G Y Q G 3 106 G
G Y Q G R V F L 3 134 Y G R Y K C E V I 3 154 L D L Q G V V F P 3
160 V F P Y F P R L G 3 163 Y F P R L G R Y N 3 165 P R L G R Y N L
N 3 169 R Y N L N F H E A 3 203 D W C N A G W L S 3 223 R E P C G G
Q N T 3 224 E P C G G Q N T V 3 228 G Q N T V P G V R 3 236 R N Y G
F W D K D 3 252 C F T S N F N G R 3 257 F N G R F Y Y L I 3 279 C L
N D G A Q I A 3 285 Q I A K V G Q I F 3 288 K V G Q I F A A W 3 302
D R C D A G W L A 3 313 S V R Y P I S R P 3 319 S R P R R R C S P 3
329 E A A V R F V G F 3 333 R F V G F P D K K 3 342 H K L Y G V Y C
F 3 8 V L I S I C W A D 2 19 S D N Y T L D H D 2 38 P H L L V E A E
Q 2 44 A E Q A K V F S H 2 49 V F S H R G G N V 2 55 G N V T L P C
K F 2 60 P C K F Y R D P T 2 63 F Y R D P T A F G 2 70 F G S G I H
K I R 2 72 S G I H K I R I K 2 76 K I R I K W T K L 2 77 I R I K W
T K L T 2 82 T K L T S D Y L K 2 86 S D Y L K E V D V 2 87 D Y L K
E V D V F 2 94 V F V S M G Y H K 2 101 H K K T Y G G Y Q 2 104 T Y
G G Y Q G R V 2 121 D A S L V I T D L 2 124 L V I T D L T L E 2 140
E V I E G L E D D 2 149 T V V V A L D L Q 2 152 V A L D L Q G V V 2
170 Y N L N F H E A Q 2 191 F D Q L Y D A W R 2 208 G W L S D G S V
Q 2 212 D G S V Q Y P I T 2 217 Y P I T K P R E P 2 218 P I T K P R
E P C 2 229 Q N T V P G V R N 2 232 V P G V R N Y G F 2 234 G V R N
Y G F W D 2 251 F C F T S N F N G 2 269 K L T Y D E A V Q 2 276 V Q
A C L N D G A 2 278 A C L N D G A Q I 2 284 A Q I A K V G Q I 2 290
G Q I F A A W K I 2 295 A W K I L G Y D R 2 296 W K I L G Y D R C 2
297 K I L G Y D R C D 2 298 I L G Y D R C D A 2 301 Y D R C D A G W
L 2 307 G W L A D G S V R 2 316 Y P I S R P R R R 2 317 P I S R P R
R R C 2 326 S P T E A A V R F 2 330 A A V R F V G F P 2 336 G F P D
K K H K L 2 341 K H K L Y G V Y C 2 5 L L L V L I S I C 1 15 A D H
L S D N Y T 1 16 D H L S D N Y T L 1 31 H I Q A E N G P H 1 32 I Q
A E N G P H L 1 37 G P H L L V E A E 1 39 H L L V E A E Q A 1 40 L
L V E A E Q A K 1 47 A K V F S H R G G 1 48 K V F S H R G G N 1 66
D P T A F G S G I 1 111 R V F L K G G S D 1 114 L K G G S D S D A 1
128 D L T L E D Y G R 1 132 E D Y G R Y K C E 1 133 D Y G R Y K C E
V 1 143 E G L E D D T V V 1 151 V V A L D L Q G V 1 158 G V V F P Y
F P R 1 168 G R Y N L N F H E 1 171 N L N F H E A Q Q 1 177 A Q Q A
C L D Q D 1 193 Q L Y D A W R G G 1 198 W R G G L D W C N 1 205 C N
A G W L S D G 1 207 A G W L S D G S V 1 221 K P R E P C G G Q 1 227
G G Q N T V P G V 1 243 K D K S R Y D V F 1 244 D K S R Y D V F C 1
250 V F C F T S N F N 1 261 F Y Y L I H P T K 1 268 T K L T Y D E A
V 1 275 A V Q A C L N D G 1 282 D G A Q I A K V G 1 289 V G Q I F A
A W K 1 294 A A W K I L G Y D 1 304 C D A G W L A D G 1 306 A G W L
A D G S V 1 315 R Y P I S R P R R 1 323 R R C S P T E A A 1 344 L Y
G V Y C F R A 1 346 G V Y C F R A Y N 1 151P3D4 v.2: HLA Peptide
Scoring Results A1 9-mers SYFPEITHI 188 R K E K A E I H Y 29 123 N
T N P S R R P Y 26 367 P A D L A G S G Y 26 106 S F C R N K L K Y
25 59 F V G S Y K L A Y 23 302 S T Y D S L S P Y 23 169 A P H E V G
W K Y 21 220 Y T E S P G G G S 20 83 R K D K V L L G R 18 97 S C E
G I N I S G 18 157 A S E A Y K K V C 17 212 N M K K K I D K Y 17
296 S C P T S S S T Y 17 55 G H V Q F V G S Y 16 69 N D G E H W T V
Y 16 323 P S G G G G L K K 16 353 P K S E N N S W Y 16 153 P Q G H
A S E A Y 15 361 Y V E N G R P A D 15 385 S L E E G L G G K 15 77 Y
Q D E K Q R K D 14 354 K S E N N S W Y V 14 386 L E E G L G G K Q
14 400 K A E N G P H L L 14 7 K T F P L R A L H 13 21 I R D H S G Q
K M 13 30 K Q D K K V D L L 13 51 A K D F G H V Q F 13 68 S N D G E
H W T V 13 78 Q D E K Q R K D K 13 145 K A D G G S C C P 13 5 T T K
T F P L R A 12 17 V V E S I R D H S 12 170 P H E V G W K Y Q 12 183
T L E E K R K E K 12 184 L E E K R K E K A 12 191 K A E I H Y R K N
12 208 Q A E K N M K K K 12 244 A T R A T R I G H 12 264 A H R P P
A L S A 12 301 S S T Y D S L S P 12 1 M L E H T T K T F 11 4 H T T
K T F P L R 11 34 K V D L L V P T K 11 40 P T K V T G I I T 11 216
K I D K Y T E S P 11 226 G G S P R G L G F 11 279 A S P A A W L P L
11 382 A I E S L E E G L 11 384 E S L E E G L G G 11 394 Q K D K E
R K A E 11 31 Q D K K V D L L V 10 70 D G E H W T V Y Q 10 74 W T V
Y Q D E K Q 10 133 F Q V P S R I F W 10 142 R Q E K A D G G S 10
291 W T R P S S C P T 10 295 S S C P T S S S T 10 303 T Y D S L S P
Y G 10 364 N G R P A D L A G 10 373 S G Y C G A L W K 10 396 D K E
R K A E N G 10 82 Q R K D K V L L G 9 112 L K Y L A F L H K 9 150 S
C C P Q G H A S 9 160 A Y K K V C L S G 9 180 V T A T L E E K R 9
182 A T L E E K R K E 9 196 Y R K N K Q L M R 9 229 P R G L G F I F
K 9 247 A T R I G H P G G 9 300 S S S T Y D S L S 9 306 S L S P Y G
P R N 9 67 Y S N D G E H W T 8 222 E S P G G G S P R 8 310 Y G P R
N P L P N 8 322 S P S G G G G L K 8 32 D K K V D L L V P 7 43 V T G
I I T Q G A 7 47 I T Q G A K D F G 7 96 V S C E G I N I S 7 105 G S
F C R N K L K 7 127 S R R P Y H F Q V 7 199 N K Q L M R L Q K 7 221
T E S P G G G S P 7 236 F K T I A P L A A 7 237 K T I A P L A A T 7
250 I G H P G G R T P 7 256 R T P R A G S S A 7 272 A R A P V P A A
S 7 278 A A S P A A W L P 7 288 R T P W T R P S S 7 309 P Y G P R N
P L P 7 321 H S P S G G G G L 7 324 S G G G G L K K P 7 338 G Q K H
N V L A R 7 346 R G K P Q R K P K 7 372 G S G Y C G A L W 7 8 T F P
L R A L H I 6 10 P L R A L H I V V 6 41 T K V T G I I T Q 6 54 F G
H V Q F V G S 6 95 V V S C E G I N I 6 109 R N K L K Y L A F 6 166
L S G A P H E V G 6 167 S G A P H E V G W 6 178 Q A V T A T L E E 6
227 G S P R G L G F I 6 262 S S A H R P P A L 6 281 P A A W L P L R
T 6 283 A W L P L R T P W 6 298 P T S S S T Y D S 6 307 L S P Y G P
R N P 6 333 A R H C Q G Q K H 6 358 N S W Y V E N G R 6 380 W K A I
E S L E E 6 13 A L H I V V E S I 5 23 D H S G Q K M K Q 5 35 V D L
L V P T K V 5 37 L L V P T K V T G 5 45 G I I T Q G A K D 5 57 V Q
F V G S Y K L 5 104 S G S F C R N K L 5 126 P S R R P Y H F Q 5 149
G S C C P Q G H A 5 204 R L Q K Q A E K N 5 223 S P G G G S P R G 5
261 G S S A H R P P A 5 263 S A H R P P A L S 5 274 A P V P A A S P
A 5 294 P S S C P T S S S 5 305 D S L S P Y G P R 5 308 S P Y G P R
N P L 5 320 R H S P S G G G G 5 329 L K K P A R H C Q 5 388 E G L G
G K Q K D 5 15 H I V V E S I R D 4 19 E S I R D H S G Q 4 24 H S G
Q K M K Q D 4 27 Q K M K Q D K K V 4 61 G S Y K L A Y S N 4 87 V L
L G R K A V V 4 102 N I S G S F C R N 4 103 I S G S F C R N K 4 128
R R P Y H F Q V P 4 131 Y H F Q V P S R I 4 135 V P S R I F W R Q 4
136 P S R I F W R Q E 4 177 Y Q A V T A T L E 4 211 K N M K K K I D
K 4 225 G G G S P R G L G 4 228 S P R G L G F I F 4 231 G L G F I F
K T I 4 233 G F I F K T I A P 4 238 T I A P L A A T R 4 251 G H P G
G R T P R 4 255 G R T P R A G S S 4 265 H R P P A L S A R 4 270 L S
A R A P V P A 4 271 S A R A P V P A A 4 280 S P A A W L P L R 4 287
L R T P W T R P S 4 299 T S S S T Y D S L 4 312 P R N P L P N P R 4
314 N P L P N P R H S 4 316 L P N P R H S P S 4 343 V L A R G K P Q
R 4 345 A R G K P Q R K P 4 350 Q R K P K S E N N 4 377 G A L W K A
I E S 4 390 L G G K Q K D K E 4 22 R D H S G Q K M K 3 36 D L L V P
T K V T 3 39 V P T K V T G I I 3 49 Q G A K D F G H V 3 53 D F G H
V Q F V G 3 56 H V Q F V G S Y K 3 58 Q F V G S Y K L A 3 63 Y K L
A Y S N D G 3 85 D K V L L G R K A 3 86 K V L L G R K A V 3 90 G R
K A V V V S C 3 91 R K A V V V S C E 3 111 K L K Y L A F L H 3 114
Y L A F L H K R M 3 130 P Y H F Q V P S R 3 137 S R I F W R Q E K 3
144 E K A D G G S C C 3 159 E A Y K K V C L S 3 164 V C L S G A P H
E 3 173 V G W K Y Q A V T 3 192 A E I H Y R K N K 3 207 K Q A E K N
M K K 3 209 A E K N M K K K I 3 230 R G L G F I F K T 3 269 A L S A
R A P V P 3 315 P L P N P R H S P 3 335 H C Q G Q K H N V 3 337 Q G
Q K H N V L A 3 341 H N V L A R G K P 3 355 S E N N S W Y V E 3 359
S W Y V E N G R P 3 363 E N G R P A D L A 3 368 A D L A G S G Y C 3
369 D L A G S G Y C G 3 371 A G S G Y C G A L 3 374 G Y C G A L W K
A 3 387 E E G L G G K Q K 3 14 L H I V V E S I R 2 20 S I R D H S G
Q K 2 25 S G Q K M K Q D K 2 26 G Q K M K Q D K K 2 46 I I T Q G A
K D F 2 50 G A K D F G H V Q 2 52 K D F G H V Q F V 2 62 S Y K L A
Y S N D 2 64 K L A Y S N D G E 2 66 A Y S N D G E H W 2 72 E H W T
V Y Q D E 2 79 D E K Q R K D K V 2 81 K Q R K D K V L L 2 88 L L G
R K A V V V 2 89 L G R K A V V V S 2 92 K A V V V S C E G 2 101 I N
I S G S F C R 2 108 C R N K L K Y L A 2 113 K Y L A F L H K R 2 116
A F L H K R M N T 2 117 F L H K R M N T N 2 138 R I F W R Q E K A 2
139 I F W R Q E K A D 2 146 A D G G S C C P Q 2 151 C C P Q G H A S
E 2 155 G H A S E A Y K K 2 156 H A S E A Y K K V 2 158 S E A Y K K
V C L 2 161 Y K K V C L S G A 2 165 C L S G A P H E V 2 174 G W K Y
Q A V T A 2 176 K Y Q A V T A T L 2 193 E I H Y R K N K Q 2 195 H Y
R K N K Q L M 2 197 R K N K Q L M R L 2 198 K N K Q L M R L Q 2 200
K Q L M R L Q K Q 2 202 L M R L Q K Q A E 2 235 I F K T I A P L A 2
241 P L A A T R A T R 2 249 R I G H P G G R T 2 254 G G R T P R A G
S 2 257 T P R A G S S A H 2 282 A A W L P L R T P 2 286 P L R T P W
T R P 2 304 Y D S L S P Y G P 2 313 R N P L P N P R H 2 328 G L K K
P A R H C 2 334 R H C Q G Q K H N 2 339 Q K H N V L A R G 2 347 G K
P Q R K P K S 2 357 N N S W Y V E N G 2 362 V E N G R P A D L 2 370
L A G S G Y C G A 2 375 Y C G A L W K A I 2 378 A L W K A I E S L 2
379 L W K A I E S L E 2 383 I E S L E E G L G 2 389 G L G G K Q K D
K 2 393 K Q K D K E R K A 2 6 T K T F P L R A L 1 9 F P L R A L H I
V 1 11 L R A L H I V V E 1 12 R A L H I V V E S 1 18 V E S I R D H
S G 1 28 K M K Q D K K V D 1 38 L V P T K V T G I 1 42 K V T G I I
T Q G 1 60 V G S Y K L A Y S 1 71 G E H W T V Y Q D 1 73 H W T V Y
Q D E K 1 76 V Y Q D E K Q R K 1 80 E K Q R K D K V L 1 93 A V V V
S C E G I 1 94 V V V S C E G I N 1 100 G I N I S G S F C 1 107 F C
R N K L K Y L 1 110 N K L K Y L A F L 1 115 L A F L H K R M N 1 118
L H K R M N T N P 1 120 K R M N T N P S R 1 122 M N T N P S R R P 1
124 T N P S R R P Y H 1 132 H F Q V P S R I F 1 140 F W R Q E K A D
G 1 143 Q E K A D G G S C 1 152 C P Q G H A S E A 1 163 K V C L S G
A P H 1 168 G A P H E V G W K 1 171 H E V G W K Y Q A 1 175 W K Y Q
A V T A T 1 179 A V T A T L E E K 1 194 I H Y R K N K Q L 1 201 Q L
M R L Q K Q A 1 206 Q K Q A E K N M K 1 224 P G G G S P R G
L 1 234 F I F K T I A P L 1 240 A P L A A T R A T 1 243 A A T R A T
R I G 1 246 R A T R I G H P G 1 248 T R I G H P G G R 1 252 H P G G
R T P R A 1 258 P R A G S S A H R 1 260 A G S S A H R P P 1 268 P A
L S A R A P V 1 273 R A P V P A A S P 1 276 V P A A S P A A W 1 277
P A A S P A A W L 1 284 W L P L R T P W T 1 290 P W T R P S S C P 1
311 G P R N P L P N P 1 319 P R H S P S G G G 1 325 G G G G L K K P
A 1 336 C Q G Q K H N V L 1 342 N V L A R G K P Q 1 344 L A R G K P
Q R K 1 349 P Q R K P K S E N 1 352 K P K S E N N S W 1 360 W Y V E
N G R P A 1 398 E R K A E N G P H 1 399 R K A E N G P H L 1
[0823]
30TABLE XXIII SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:
HLA Peptide Scoring Results A*0201 9-mers SYFPEITHI 4 L L L L V L I
S I 28 88 Y L K E V D V F V 25 123 S L V I T D L T L 25 144 G L E D
D T V V V 25 84 L T S D Y L K E V 23 76 K I R I K W T K L 22 151 V
V A L D L Q G V 22 3 S L L L L V L I S 20 51 S H R G G N V T L 20
159 V V F P Y F P R L 20 263 Y L I H P T K L T 20 5 L L L V L I S I
C 19 41 L V E A E Q A K V 19 69 A F G S G I H K I 19 137 Y K C E V
I E G L 19 152 V A L D L Q G V V 19 2 K S L L L L V L I 18 22 Y T L
D H D R A I 18 186 A V I A S F D Q L 18 279 C L N D G A Q I A 18
281 N D G A Q I A K V 18 291 Q I F A A W K I L 18 32 I Q A E N G P
H L 17 34 A E N G P H L L V 17 121 D A S L V I T D L 17 227 G G Q N
T V P G V 17 284 A Q I A K V G Q I 17 308 W L A D G S V R Y 17 1 M
K S L L L L V L 16 7 L V L I S I C W A 16 33 Q A E N G P H L L 16
39 H L L V E A E Q A 16 86 S D Y L K E V D V 16 106 G G Y Q G R V F
L 16 113 F L K G G S D S D 16 116 G G S D S D A S L 16 181 C L D Q
D A V I A 16 262 Y Y L I H P T K L 16 336 G F P D K K H K L 16 40 L
L V E A E Q A K 15 125 V I T D L T L E D 15 141 V I E G L E D D T
15 155 D L Q G V V F P Y 15 179 Q A C L D Q D A V 15 180 A C L D Q
D A V I 15 207 A G W L S D G S V 15 209 W L S D G S V Q Y 15 264 L
I H P T K L T Y 15 298 I L G Y D R C D A 15 306 A G W L A D G S V
15 324 R C S P T E A A V 15 339 D K K H K L Y G V 15 8 V L I S I C
W A D 14 10 I S I C W A D H L 14 16 D H L S D N Y T L 14 142 I E G
L E D D T V 14 146 E D D T V V V A L 14 148 D T V V V A L D L 14
153 A L D L Q G V V F 14 164 F P R L G R Y N L 14 201 G L D W C N A
G W 14 224 E P C G G Q N T V 14 256 N F N G R F Y Y L 14 268 T K L
T Y D E A V 14 270 L T Y D E A V Q A 14 278 A C L N D G A Q I 14
293 F A A W K I L G Y 14 297 K I L G Y D R C D 14 327 P T E A A V R
F V 14 343 K L Y G V Y C F R 14 36 N G P H L L V E A 13 81 W T K L
T S D Y L 13 83 K L T S D Y L K E 13 104 T Y G G Y Q G R V 13 145 L
E D D T V V V A 13 189 A S F D Q L Y D A 13 193 Q L Y D A W R G G
13 194 L Y D A W R G G L 13 202 L D W C N A G W L 13 272 Y D E A V
Q A C L 13 287 A K V G Q I F A A 13 6 L L V L I S I C W 12 9 L I S
I C W A D H 12 23 T L D H D R A I H 12 58 T L P C K F Y R D 12 118
S D S D A S L V I 12 124 L V I T D L T L E 12 133 D Y G R Y K C E V
12 154 L D L Q G V V F P 12 166 R L G R Y N L N F 12 171 N L N F H
E A Q Q 12 174 F H E A Q Q A C L 12 187 V I A S F D Q L Y 12 214 S
V Q Y P I T K P 12 230 N T V P G V R N Y 12 290 G Q I F A A W K I
12 301 Y D R C D A G W L 12 309 L A D G S V R Y P 12 11 S I C W A D
H L S 11 17 H L S D N Y T L D 11 24 L D H D R A I H I 11 49 V F S H
R G G N V 11 73 G I H K I R I K W 11 103 K T Y G G Y Q G R 11 117 G
S D S D A S L V 11 120 S D A S L V I T D 11 130 T L E D Y G R Y K
11 140 E V I E G L E D D 11 143 E G L E D D T V V 11 211 S D G S V
Q Y P I 11 257 F N G R F Y Y L I 11 269 K L T Y D E A V Q 11 275 A
V Q A C L N D G 11 286 I A K V G Q I F A 11 294 A A W K I L G Y D
11 310 A D G S V R Y P I 11 330 A A V R F V G F P 11 28 R A I H I Q
A E N 10 29 A I H I Q A E N G 10 78 R I K W T K L T S 10 79 I K W T
K L T S D 10 90 K E V D V F V S M 10 95 F V S M G Y H K K 10 96 V S
M G Y H K K T 10 97 S M G Y H K K T Y 10 122 A S L V I T D L T 10
126 I T D L T L E D Y 10 128 D L T L E D Y G R 10 129 L T L E D Y G
R Y 10 134 Y G R Y K C E V I 10 197 A W R G G L D W C 10 242 D K D
K S R Y D V 10 260 R F Y Y L I H P T 10 285 Q I A K V G Q I F 10
304 C D A G W L A D G 10 313 S V R Y P I S R P 10 44 A E Q A K V F
S H 9 57 V T L P C K F Y R 9 71 G S G I H K I R I 9 72 S G I H K I
R I K 9 77 I R I K W T K L T 9 119 D S D A S L V I T 9 276 V Q A C
L N D G A 9 346 G V Y C F R A Y N 9 31 H I Q A E N G P H 8 50 F S H
R G G N V T 8 66 D P T A F G S G I 8 74 I H K I R I K W T 8 111 R V
F L K G G S D 8 114 L K G G S D S D A 8 149 T V V V A L D L Q 8 169
R Y N L N F H E A 8 182 L D Q D A V I A S 8 205 C N A G W L S D G 8
210 L S D G S V Q Y P 8 219 I T K P R E P C G 8 246 S R Y D V F C F
T 8 283 G A Q I A K V G Q 8 288 K V G Q I F A A W 8 323 R R C S P T
E A A 8 342 H K L Y G V Y C F 8 13 C W A D H L S D N 7 15 A D H L S
D N Y T 7 37 G P H L L V E A E 7 48 K V F S H R G G N 7 54 G G N V
T L P C K 7 61 C K F Y R D P T A 7 63 F Y R D P T A F G 7 68 T A F
G S G I H K 7 107 G Y Q G R V F L K 7 150 V V V A L D L Q G 7 172 L
N F H E A Q Q A 7 178 Q Q A C L D Q D A 7 183 D Q D A V I A S F 7
196 D A W R G G L D W 7 217 Y P I T K P R E P 7 231 T V P G V R N Y
G 7 249 D V F C F T S N F 7 265 I H P T K L T Y D 7 271 T Y D E A V
Q A C 7 344 L Y G V Y C F R A 7 12 I C W A D H L S D 6 18 L S D N Y
T L D H 6 19 S D N Y T L D H D 6 27 D R A I H I Q A E 6 30 I H I Q
A E N G P 6 52 H R G G N V T L P 6 91 E V D V F V S M G 6 99 G Y H
K K T Y G G 6 131 L E D Y G R Y K C 6 167 L G R Y N L N F H 6 170 Y
N L N F H E A Q 6 177 A Q Q A C L D Q D 6 188 I A S F D Q L Y D 6
200 G G L D W C N A G 6 204 W C N A G W L S D 6 206 N A G W L S D G
S 6 223 R E P C G G Q N T 6 234 G V R N Y G F W D 6 236 R N Y G F W
D K D 6 253 F T S N F N G R F 6 259 G R F Y Y L I H P 6 267 P T K L
T Y D E A 6 317 P I S R P R R R C 6 322 R R R C S P T E A 6 329 E A
A V R F V G F 6 334 F V G F P D K K H 6 14 W A D H L S D N Y 5 46 Q
A K V F S H R G 5 64 Y R D P T A F G S 5 87 D Y L K E V D V F 5 89
L K E V D V F V S 5 108 Y Q G R V F L K G 5 109 Q G R V F L K G G 5
112 V F L K G G S D S 5 136 R Y K C E V I E G 5 158 G V V F P Y F P
R 5 215 V Q Y P I T K P R 5 218 P I T K P R E P C 5 221 K P R E P C
G G Q 5 238 Y G F W D K D K S 5 239 G F W D K D K S R 5 255 S N F N
G R F Y Y 5 261 F Y Y L I H P T K 5 277 Q A C L N D G A Q 5 280 L N
D G A Q I A K 5 299 L G Y D R C D A G 5 305 D A G W L A D G S 5 326
S P T E A A V R F 5 331 A V R F V G F P D 5 332 V R F V G F P D K 5
333 R F V G F P D K K 5 25 D H D R A I H I Q 4 26 H D R A I H I Q A
4 35 E N G P H L L V E 4 42 V E A E Q A K V F 4 55 G N V T L P C K
F 4 67 P T A F G S G I H 4 75 H K I R I K W T K 4 93 D V F V S M G
Y H 4 135 G R Y K C E V I E 4 147 D D T V V V A L D 4 161 F P Y F P
R L G R 4 162 P Y F P R L G R Y 4 190 S F D Q L Y D A W 4 191 F D Q
L Y D A W R 4 195 Y D A W R G G L D 4 199 R G G L D W C N A 4 212 D
G S V Q Y P I T 4 213 G S V Q Y P I T K 4 226 C G G Q N T V P G 4
245 K S R Y D V F C F 4 289 V G Q I F A A W K 4 292 I F A A W K I L
G 4 296 W K I L G Y D R C 4 300 G Y D R C D A G W 4 302 D R C D A G
W L A 4 303 R C D A G W L A D 4 312 G S V R Y P I S R 4 314 V R Y P
I S R P R 4 316 Y P I S R P R R R 4 318 I S R P R R R C S 4 319 S R
P R R R C S P 4 320 R P R R R C S P T 4 21 N Y T L D H D R A 3 38 P
H L L V E A E Q 3 53 R G G N V T L P C 3 56 N V T L P C K F Y 3 59
L P C K F Y R D P 3 62 K F Y R D P T A F 3 80 K W T K L T S D Y 3
82 T K L T S D Y L K 3 127 T D L T L E D Y G 3 139 C E V I E G L E
D 3 156 L Q G V V F P Y F 3 163 Y F P R L G R Y N 3 168 G R Y N L N
F H E 3 173 N F H E A Q Q A C 3 185 D A V I A S F D Q 3 198 W R G G
L D W C N 3 208 G W L S D G S V Q 3 232 V P G V R N Y G F 3 235 V R
N Y G F W D K 3 247 R Y D V F C F T S 3 248 Y D V F C F T S N 3 266
H P T K L T Y D E 3 295 A W K I L G Y D R 3 307 G W L A D G S V R 3
335 V G F P D K K H K 3 341 K H K L Y G V Y C 3 20 D N Y T L D H D
R 2 43 E A E Q A K V F S 2 47 A K V F S H R G G 2 65 R D P T A F G
S G 2 70 F G S G I H K I R 2 94 V F V S M G Y H K 2 98 M G Y H K K
T Y G 2 100 Y H K K T Y G G Y 2 102 K K T Y G G Y Q G 2 110 G R V F
L K G G S 2 115 K G G S D S D A S 2 157 Q G V V F P Y F P 2 165 P R
L G R Y N L N 2 175 H E A Q Q A C L D 2 176 E A Q Q A C L D Q 2 184
Q D A V I A S F D 2 228 G Q N T V P G V R 2 229 Q N T V P G V R N 2
244 D K S R Y D V F C 2 251 F C F T S N F N G 2 274 E A V Q A C L N
D 2 325 C S P T E A A V R 2 328 T E A A V R F V G 2 340 K K H K L Y
G V Y 2 345 Y G V Y C F R A Y 2 92 V D V F V S M G Y 1 105 Y G G Y
Q G R V F 1 160 V F P Y F P R L G 1 216 Q Y P I T K P R E 1 220 T K
P R E P C G G 1 240 F W D K D K S R Y 1 241 W D K D K S R Y D 1 250
V F C F T S N F N 1 252 C F T S N F N G R 1 258 N G R F Y Y L I H 1
273 D E A V Q A C L N 1 315 R Y P I S R P R R 1 337 F P D K K H K L
Y 1 45 E Q A K V F S H R -1 132 E D Y G R Y K C E -1 203 D W C N A
G W L S -1 225 P C G G Q N T V P -1 222 P R E P C G G Q N -2 237 N
Y G F W D K D K -2 233 P G V R N Y G F W -3 338 P D K K H K L Y G
-3 151P3D4 v.2: HLA Peptide Scoring Results A*0201 9-mers SYFPEITHI
378 A L W K A I E S L 29 87 V L L G R K A V V 27 13 A L H I V V E S
I 26 234 F I F K T I A P L 26 88 L L G R K A V V V 25 165 C L S G A
P H E V 25 382 A I E S L E E G L 21 38 L V P T K V T G I 20 385 S L
E E G L G G K 20 86 K V L L G R K A V 19 110 N K L K Y L A F L 19
231 G L G F I F K T I 19 237 K T I A P L A A T 19 9 F P L R A L H I
V 18 10 P L R A L H I V V 18 37 L L V P T K V T G 18 52 K D F G H V
Q F V 18 36 D L L V P T K V T 17 57 V Q F V G S Y K L 17 114 Y L A
F L H K R M 17 156 H A S E A Y K K V 17 176 K Y Q A V T A T L 17
238 T I A P L A A T R 17 271 S A R A P V P A A 17 284 W L P L R T P
W T 17 308 S P Y G P R N P L 17 400 K A E N G P H L L 17 30 K Q D K
K V D L L 16 68 S N D G E H W T V 16 158 S E A Y K K V C L 16 242 L
A A T R A T R I 16 262 S S A H R P P A L 16 277 P A A S P A A W L
16 306 S L S P Y G P R N 16 343 V L A R G K P Q R 16 362 V E N G R
P A D L 16 371 A G S G Y C G A L 16 35 V D L L V P T K V 15 45 G I
I T Q G A K D 15 93 A V V V S C E G I 15 107 F C R N K L K Y L 15
127 S R R P Y H F Q V 15 138 R I F W R Q E K A 15 197 R K N K Q L M
R L 15 201 Q L M R L Q K Q A 15 227 G S P R G L G F I 15 230 R G L
G F I F K T 15 268 P A L S A R A P V 15 381 K A I E S L E E G 15
399 R K A E N G P H L 15 6 T K T F P L R A L 14 12 R A L H I V V E
S 14 29 M K Q D K K V D L 14 104 S G S F C R N K L 14 117 F L H K R
M N T N 14 212 N M K K K I D K Y 14 216 K I D K Y T E S P 14 282 A
A W L P L R T P 14 369 D L A G S G Y C G 14 33 K K V D L L V P T 13
34 K V D L L V P T K 13 64 K L A Y S N D G E 13 81 K Q R K D K V L
L 13 95 V V S C E G I N I 13 172 E V G W K Y Q A V 13 183 T L E E K
R K E K 13 194 I H Y R K N K Q L 13 241 P L A A T R A T R 13 249 R
I G H P G G R T 13 269 A L S A R A P V P 13 279 A S P A A W L P L
13 321 H S P S G G G G L 13 335 H C Q G Q K H N V 13 370 L A G S G
Y C G A 13 374 G Y C G A L W K A 13 389 G L G G K Q K D K 13 1 M L
E H T T K T F 12 16 I V V E S I R D H 12 27 Q K M K Q D K K V 12 43
V T G I I T Q G A 12 49 Q G A K D F G H V 12 182 A T L E E K R K E
12 204 R L Q K Q A E K N 12 264 A H R P P A L S A 12 299 T S S S T
Y D S L 12 302 S T Y D S L S P Y 12 336 C Q G Q K H N V L 12 7 K T
F P L R A L H 11 20 S I R D H S G Q K 11 67 Y S N D G E H W T 11
113 K Y L A F L H K R 11 131 Y H F Q V P S R I 11 179 A V T A T L E
E K 11 202 L M R L Q K Q A E 11 240 A P L A A T R A T 11 315 P L P
N P R H S P 11 324 S G G G G L K K P 11 328 G L K K P A R H C 11
375 Y C G A L W K A I 11 11 L R A L H I V V E 10 31 Q D K K V D L L
V 10 39 V P T K V T G I I 10 42 K V T G I I T Q G 10 46 I I T Q G A
K D F 10 79 D E K Q R K D K V 10 96 V S C E G I N I S 10 100 G I N
I S G S F C 10 102 N I S G S F C R N 10 111 K L K Y L A F L H 10
161 Y K K V C L S G A 10 175 W K Y Q A V T A T 10 180 V T A T L E E
K R 10 209 A E K N M K K K I 10 224 P G G G S P R G L 10 239 I A P
L A A T R A 10 247 A T R I G H P G G 10 256 R T P R A G S S A 10
270 L S A R A P V P A 10 291 W T R P S S C P T 10 295 S S C P T S S
S T 10 354 K S E N N S W Y V 10 377 G A L W K A I E S 10 3 E H T T
K T F P L 9 5 T T K T F P L R A 9 8 T F P L R A L H I 9 65 L A Y S
N D G E H 9 116 A F L H K R M N T 9 121 R M N T N P S R R 9 145 K A
D G G S C C P 9 167 S G A P H E V G W 9 168 G A P H E V G W K 9 173
V G W K Y Q A V T 9 178 Q A V T A T L E E 9 186 E K R K E K A E I 9
200 K Q L M R L Q K Q 9 252 H P G G R T P R A 9 263 S A H R P P A L
S 9 272 A R A P V P A A S 9 273 R A P V P A A S P 9 280 S P A A W L
P L R 9 281 P A A W L P L R T 9 344 L A R G K P Q R K 9 361 Y V E N
G R P A D 9 15 H I V V E S I R D 8 21 I R D H S G Q K M 8 41 T K V
T G I I T Q 8 47 I T Q G A K D F G 8 55 G H V Q F V G S Y 8 59 F V
G S Y K L A Y 8 89 L G R K A V V V S 8 90 G R K A V V V S C 8 134 Q
V P S R I F W R 8 152 C P Q G H A S E A 8 207 K Q A E K N M K K 8
232 L G F I F K T I A 8 250 I G H P G G R T P 8 274 A P V P A A S P
A 8 278 A A S P A A W L P 8 286 P L R T P W T R P 8 365 G R P A D L
A G S 8 393 K Q K D K E R K A 8 28 K M K Q D K K V D 7 50 G A K D F
G H V Q 7 60 V G S Y K L A Y S 7 77 Y Q D E K Q R K D 7 80 E K Q R
K D K V L 7 92 K A V V V S C E G 7 108 C R N K L K Y L A 7 115 L A
F L H K R M N 7 123 N T N P S R R P Y 7 159 E A Y K K V C L S 7 163
K V C L S G A P H 7 171 H E V G W K Y Q A 7 174 G W K Y Q A V T A 7
184 L E E K R K E K A 7 193 E I H Y R K N K Q 7 203 M R L Q K Q A E
K 7 215 K K I D K Y T E S 7 220 Y T E S P G G G S 7 223 S P G G G S
P R G 7 243 A A T R A T R I G 7 244 A T R A T R I G H 7 265 H R P P
A L S A R 7 266 R P P A L S A R A 7 275 P V P A A S P A A 7 283 A W
L P L R T P W 7 288 R T P W T R P S S 7 311 G P R N P L P N P 7 325
G G G G L K K P A 7 61 G S Y K L A Y S N 6 63 Y K L A Y S N D G 6
71 G E H W T V Y Q D 6 82 Q R K D K V L L G 6 83 R K D K V L L G R
6 85 D K V L L G R K A 6 91 R K A V V V S C E 6 101 I N I S G S F C
R 6 149 G S C C P Q G H A 6 150 S C C P Q G H A S 6 151 C C P Q G H
A S E 6 155 G H A S E A Y K K 6 164 V C L S G A P H E 6 169 A P H E
V G W K Y 6 191 K A E I H Y R K N 6 221 T E S P G G G S P 6 233 G F
I F K T I A P 6 235 I F K T I A P L A 6 236 F K T I A P L A A 6 245
T R A T R I G H P 6 261 G S S A H R P P A 6 276 V P A A S P A A W 6
285 L P L R T P W T R 6 322 S P S G G G G L K 6 327 G G L K K P A R
H 6 337 Q G Q K H N V L A 6 338 G Q K H N V L A R 6 339 Q K H N V L
A R G 6 360 W Y V E N G R P A 6 366 R P A D L A G S G 6 368 A D L A
G S G Y C 6 373 S G Y C G A L W K 6 386 L E E G L G G K Q 6 395 K D
K E R K A E N 6 51 A K D F G H V Q F 5 58 Q F V G S Y K L A 5 74 W
T V Y Q D E K Q 5 84 K D K V L L G R K 5 94 V V V S C E G I N 5 97
S C E G I N I S G 5 98 C E G I N I S G S 5 106 S F C R N K L K Y 5
120 K R M N T N P S R 5 137 S R I F W R Q E K 5 189 K E K A E I H Y
R 5 226 G G S P R G L G F 5 228 S P R G L G F I F 5 248 T R I G H P
G G R 5 251 G H P G G R T P R 5 254 G G R T P R A G S 5 259 R A G S
S A H R P 5 287 L R T P W T R P S 5 316 L P N P R H S P S 5 342 N V
L A R G K P Q 5 345 A R G K P Q R K P 5 357 N N S W Y V E N G 5 380
W K A I E S L E E 5 388 E G L G G K Q K D 5 4 H T T K T F P L R 4
14 L H I V V E S I R 4
17 V V E S I R D H S 4 18 V E S I R D H S G 4 40 P T K V T G I I T
4 54 F G H V Q F V G S 4 75 T V Y Q D E K Q R 4 112 L K Y L A F L H
K 4 129 R P Y H F Q V P S 4 141 W R Q E K A D G G 4 146 A D G G S C
C P Q 4 160 A Y K K V C L S G 4 177 Y Q A V T A T L E 4 192 A E I H
Y R K N K 4 195 H Y R K N K Q L M 4 205 L Q K Q A E K N M 4 208 Q A
E K N M K K K 4 246 R A T R I G H P G 4 255 G R T P R A G S S 4 296
S C P T S S S T Y 4 298 P T S S S T Y D S 4 304 Y D S L S P Y G P 4
314 N P L P N P R H S 4 323 P S G G G G L K K 4 326 G G G L K K P A
R 4 329 L K K P A R H C Q 4 331 K P A R H C Q G Q 4 333 A R H C Q G
Q K H 4 340 K H N V L A R G K 4 347 G K P Q R K P K S 4 355 S E N N
S W Y V E 4 364 N G R P A D L A G 4 376 C G A L W K A I E 4 390 L G
G K Q K D K E 4 23 D H S G Q K M K Q 3 26 G Q K M K Q D K K 3 32 D
K K V D L L V P 3 44 T G I I T Q G A K 3 56 H V Q F V G S Y K 3 103
I S G S F C R N K 3 119 H K R M N T N P S 3 130 P Y H F Q V P S R 3
133 F Q V P S R I F W 3 139 I F W R Q E K A D 3 140 F W R Q E K A D
G 3 162 K K V C L S G A P 3 166 L S G A P H E V G 3 187 K R K E K A
E I H 3 196 Y R K N K Q L M R 3 211 K N M K K K I D K 3 214 K K K I
D K Y T E 3 219 K Y T E S P G G G 3 257 T P R A G S S A H 3 258 P R
A G S S A H R 3 289 T P W T R P S S C 3 292 T R P S S C P T S 3 300
S S S T Y D S L S 3 301 S S T Y D S L S P 3 307 L S P Y G P R N P 3
310 Y G P R N P L P N 3 320 R H S P S G G G G 3 348 K P Q R K P K S
E 3 352 K P K S E N N S W 3 359 S W Y V E N G R P 3 384 E S L E E G
L G G 3 397 K E R K A E N G P 3 2 L E H T T K T F P 2 25 S G Q K M
K Q D K 2 48 T Q G A K D F G H 2 66 A Y S N D G E H W 2 69 N D G E
H W T V Y 2 70 D G E H W T V Y Q 2 73 H W T V Y Q D E K 2 76 V Y Q
D E K Q R K 2 109 R N K L K Y L A F 2 144 E K A D G G S C C 2 148 G
G S C C P Q G H 2 154 Q G H A S E A Y K 2 181 T A T L E E K R K 2
190 E K A E I H Y R K 2 213 M K K K I D K Y T 2 218 D K Y T E S P G
G 2 225 G G G S P R G L G 2 260 A G S S A H R P P 2 293 R P S S C P
T S S 2 294 P S S C P T S S S 2 303 T Y D S L S P Y G 2 305 D S L S
P Y G P R 2 312 P R N P L P N P R 2 313 R N P L P N P R H 2 341 H N
V L A R G K P 2 350 Q R K P K S E N N 2 356 E N N S W Y V E N 2 358
N S W Y V E N G R 2 363 E N G R P A D L A 2 367 P A D L A G S G Y 2
372 G S G Y C G A L W 2 383 I E S L E E G L G 2 391 G G K Q K D K E
R 2 22 R D H S G Q K M K 1 62 S Y K L A Y S N D 1 99 E G I N I S G
S F 1 105 G S F C R N K L K 1 118 L H K R M N T N P 1 124 T N P S R
R P Y H 1 125 N P S R R P Y H F 1 132 H F Q V P S R I F 1 135 V P S
R I F W R Q 1 143 Q E K A D G G S C 1 157 A S E A Y K K V C 1 198 K
N K Q L M R L Q 1 199 N K Q L M R L Q K 1 206 Q K Q A E K N M K 1
222 E S P G G G S P R 1 318 N P R H S P S G G 1 330 K K P A R H C Q
G 1 332 P A R H C Q G Q K 1 334 R H C Q G Q K H N 1 351 R K P K S E
N N S 1 379 L W K A I E S L E 1 392 G K Q K D K E R K 1 53 D F G H
V Q F V G -1 126 P S R R P Y H F Q -1 128 R R P Y H F Q V P -1 188
R K E K A E I H Y -1 229 P R G L G F I F K -1 297 C P T S S S T Y D
-1 319 P R H S P S G G G -1 353 P K S E N N S W Y -1 396 D K E R K
A E N G -1 72 E H W T V Y Q D E -2 78 Q D E K Q R K D K -2 136 P S
R I F W R Q E -2 153 P Q G H A S E A Y -2 210 E K N M K K K I D -2
253 P G G R T P R A G -2 387 E E G L G G K Q K -2 170 P H E V G W K
Y Q -3 185 E E K R K E K A E -3 290 P W T R P S S C P -3 398 E R K
A E N G P H -4
[0824]
31TABLE XXIV SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4: HLA
Peptide Scoring Results A*0202 9-mers SYFPEITHI NO DATA
[0825]
32TABLE XXV SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4: HLA
Peptide Scoring Results A*0203 9-mers SYFPEITHI NO DATA
[0826]
33TABLE XXVI SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:
HLA Peptide Scoring Results A3 9-mers SYFPEITHI 153 A L D L Q G V V
F 29 209 W L S D G S V Q Y 26 130 T L E D Y G R Y K 24 166 R L G R
Y N L N F 24 264 L I H P T K L T Y 24 308 W L A D G S V R Y 24 343
K L Y G V Y C F R 24 40 L L V E A E Q A K 22 95 F V S M G Y H K K
22 111 R V F L K G G S D 22 186 A V I A S F D Q L 21 75 H K I R I K
W T K 20 78 R I K W T K L T S 20 269 K L T Y D E A V Q 20 331 A V R
F V G F P D 20 123 S L V I T D L T L 19 144 G L E D D T V V V 19
155 D L Q G V V F P Y 19 261 F Y Y L I H P T K 19 285 Q I A K V G Q
I F 19 23 T L D H D R A I H 18 39 H L L V E A E Q A 18 150 V V V A
L D L Q G 18 234 G V R N Y G F W D 18 289 V G Q I F A A W K 18 307
G W L A D G S V R 18 346 G V Y C F R A Y N 18 3 S L L L L V L I S
17 56 N V T L P C K F Y 17 62 K F Y R D P T A F 17 76 K I R I K W T
K L 17 88 Y L K E V D V F V 17 113 F L K G G S D S D 17 181 C L D Q
D A V I A 17 193 Q L Y D A W R G G 17 249 D V F C F T S N F 17 288
K V G Q I F A A W 17 313 S V R Y P I S R P 17 333 R F V G F P D K K
17 4 L L L L V L I S I 16 9 L I S I C W A D H 16 51 S H R G G N V T
L 16 83 K L T S D Y L K E 16 140 E V I E G L E D D 16 171 N L N F H
E A Q Q 16 279 C L N D G A Q I A 16 5 L L L V L I S I C 15 29 A I H
I Q A E N G 15 31 H I Q A E N G P H 15 41 L V E A E Q A K V 15 48 K
V F S H R G G N 15 68 T A F G S G I H K 15 72 S G I H K I R I K 15
93 D V F V S M G Y H 15 103 K T Y G G Y Q G R 15 128 D L T L E D Y
G R 15 187 V I A S F D Q L Y 15 213 G S V Q Y P I T K 15 270 L T Y
D E A V Q A 15 275 A V Q A C L N D G 15 278 A C L N D G A Q I 15
297 K I L G Y D R C D 15 320 R P R R R C S P T 15 7 L V L I S I C W
A 14 8 V L I S I C W A D 14 91 E V D V F V S M G 14 107 G Y Q G R V
F L K 14 124 L V I T D L T L E 14 158 G V V F P Y F P R 14 231 T V
P G V R N Y G 14 243 K D K S R Y D V F 14 325 C S P T E A A V R 14
334 F V G F P D K K H 14 340 K K H K L Y G V Y 14 42 V E A E Q A K
V F 13 94 V F V S M G Y H K 13 159 V V F P Y F P R L 13 180 A C L D
Q D A V I 13 201 G L D W C N A G W 13 263 Y L I H P T K L T 13 280
L N D G A Q I A K 13 284 A Q I A K V G Q I 13 298 I L G Y D R C D A
13 326 S P T E A A V R F 13 335 V G F P D K K H K 13 17 H L S D N Y
T L D 12 44 A E Q A K V F S H 12 50 F S H R G G N V T 12 80 K W T K
L T S D Y 12 82 T K L T S D Y L K 12 125 V I T D L T L E D 12 151 V
V A L D L Q G V 12 161 F P Y F P R L G R 12 162 P Y F P R L G R Y
12 183 D Q D A V I A S F 12 208 G W L S D G S V Q 12 214 S V Q Y P
I T K P 12 235 V R N Y G F W D K 12 291 Q I F A A W K I L 12 295 A
W K I L G Y D R 12 303 R C D A G W L A D 12 317 P I S R P R R R C
12 332 V R F V G F P D K 12 341 K H K L Y G V Y C 12 6 L L V L I S
I C W 11 58 T L P C K F Y R D 11 86 S D Y L K E V D V 11 90 K E V D
V F V S M 11 97 S M G Y H K K T Y 11 102 K K T Y G G Y Q G 11 105 Y
G G Y Q G R V F 11 106 G G Y Q G R V F L 11 196 D A W R G G L D W
11 197 A W R G G L D W C 11 215 V Q Y P I T K P R 11 228 G Q N T V
P G V R 11 230 N T V P G V R N Y 11 255 S N F N G R F Y Y 11 293 F
A A W K I L G Y 11 314 V R Y P I S R P R 11 318 I S R P R R R C S
11 324 R C S P T E A A V 11 329 E A A V R F V G F 11 2 K S L L L L
V L I 10 28 R A I H I Q A E N 10 35 E N G P H L L V E 10 54 G G N V
T L P C K 10 87 D Y L K E V D V F 10 112 V F L K G G S D S 10 129 L
T L E D Y G R Y 10 141 V I E G L E D D T 10 149 T V V V A L D L Q
10 222 P R E P C G G Q N 10 236 R N Y G F W D K D 10 237 N Y G F W
D K D K 10 245 K S R Y D V F C F 10 258 N G R F Y Y L I H 10 312 G
S V R Y P I S R 10 315 R Y P I S R P R R 10 316 Y P I S R P R R R
10 321 P R R R C S P T E 10 11 S I C W A D H L S 9 12 I C W A D H L
S D 9 45 E Q A K V F S H R 9 53 R G G N V T L P C 9 57 V T L P C K
F Y R 9 73 G I H K I R I K W 9 118 S D S D A S L V I 9 126 I T D L
T L E D Y 9 145 L E D D T V V V A 9 184 Q D A V I A S F D 9 191 F D
Q L Y D A W R 9 204 W C N A G W L S D 9 218 P I T K P R E P C 9 223
R E P C G G Q N T 9 229 Q N T V P G V R N 9 240 F W D K D K S R Y 9
254 T S N F N G R F Y 9 319 S R P R R R C S P 9 322 R R R C S P T E
A 9 328 T E A A V R F V G 9 1 M K S L L L L V L 8 10 I S I C W A D
H L 8 18 L S D N Y T L D H 8 20 D N Y T L D H D R 8 26 H D R A I H
I Q A 8 34 A E N G P H L L V 8 66 D P T A F G S G I 8 67 P T A F G
S G I H 8 92 V D V F V S M G Y 8 100 Y H K K T Y G G Y 8 132 E D Y
G R Y K C E 8 134 Y G R Y K C E V I 8 135 G R Y K C E V I E 8 143 E
G L E D D T V V 8 152 V A L D L Q G V V 8 154 L D L Q G V V F P 8
177 A Q Q A C L D Q D 8 219 I T K P R E P C G 8 221 K P R E P C G G
Q 8 224 E P C G G Q N T V 8 239 G F W D K D K S R 8 247 R Y D V F C
F T S 8 260 R F Y Y L I H P T 8 282 D G A Q I A K V G 8 299 L G Y D
R C D A G 8 301 Y D R C D A G W L 8 342 H K L Y G V Y C F 8 32 I Q
A E N G P H L 7 38 P H L L V E A E Q 7 63 F Y R D P T A F G 7 65 R
D P T A F G S G 7 74 I H K I R I K W T 7 108 Y Q G R V F L K G 7
139 C E V I E G L E D 7 142 I E G L E D D T V 7 148 D T V V V A L D
L 7 164 F P R L G R Y N L 7 167 L G R Y N L N F H 7 195 Y D A W R G
G L D 7 207 A G W L S D G S V 7 225 P C G G Q N T V P 7 244 D K S R
Y D V F C 7 246 S R Y D V F C F T 7 306 A G W L A D G S V 7 330 A A
V R F V G F P 7 337 F P D K K H K L Y 7 345 Y G V Y C F R A Y 7 14
W A D H L S D N Y 6 16 D H L S D N Y T L 6 24 L D H D R A I H I 6
33 Q A E N G P H L L 6 49 V F S H R G G N V 6 61 C K F Y R D P T A
6 64 Y R D P T A F G S 6 70 F G S G I H K I R 6 79 I K W T K L T S
D 6 98 M G Y H K K T Y G 6 116 G G S D S D A S L 6 117 G S D S D A
S L V 6 119 D S D A S L V I T 6 120 S D A S L V I T D 6 146 E D D T
V V V A L 6 163 Y F P R L G R Y N 6 165 P R L G R Y N L N 6 172 L N
F H E A Q Q A 6 205 C N A G W L S D G 6 232 V P G V R N Y G F 6 253
F T S N F N G R F 6 272 Y D E A V Q A C L 6 287 A K V G Q I F A A 6
290 G Q I F A A W K I 6 296 W K I L G Y D R C 6 300 G Y D R C D A G
W 6 304 C D A G W L A D G 6 13 C W A D H L S D N 5 30 I H I Q A E N
G P 5 55 G N V T L P C K F 5 69 A F G S G I H K I 5 77 I R I K W T
K L T 5 101 H K K T Y G G Y Q 5 109 Q G R V F L K G G 5 114 L K G G
S D S D A 5 122 A S L V I T D L T 5 136 R Y K C E V I E G 5 156 L Q
G V V F P Y F 5 168 G R Y N L N F H E 5 169 R Y N L N F H E A 5 174
F H E A Q Q A C L 5 188 I A S F D Q L Y D 5 192 D Q L Y D A W R G 5
199 R G G L D W C N A 5 202 L D W C N A G W L 5 217 Y P I T K P R E
P 5 262 Y Y L I H P T K L 5 277 Q A C L N D G A Q 5 281 N D G A Q I
A K V 5 283 G A Q I A K V G Q 5 286 I A K V G Q I F A 5 292 I F A A
W K I L G 5 310 A D G S V R Y P I 5 323 R R C S P T E A A 5 15 A D
H L S D N Y T 4 22 Y T L D H D R A I 4 36 N G P H L L V E A 4 43 E
A E Q A K V F S 4 85 T S D Y L K E V D 4 89 L K E V D V F V S 4 115
K G G S D S D A S 4 138 K C E V I E G L E 4 147 D D T V V V A L D 4
170 Y N L N F H E A Q 4 175 H E A Q Q A C L D 4 179 Q A C L D Q D A
V 4 189 A S F D Q L Y D A 4 194 L Y D A W R G G L 4 200 G G L D W C
N A G 4 203 D W C N A G W L S 4 220 T K P R E P C G G 4 226 C G G Q
N T V P G 4 233 P G V R N Y G F W 4 252 C F T S N F N G R 4 256 N F
N G R F Y Y L 4 265 I H P T K L T Y D 4 273 D E A V Q A C L N 4 294
A A W K I L G Y D 4 302 D R C D A G W L A 4 338 P D K K H K L Y G 4
25 D H D R A I H I Q 3 27 D R A I H I Q A E 3 46 Q A K V F S H R G
3 47 A K V F S H R G G 3 52 H R G G N V T L P 3 104 T Y G G Y Q G R
V 3 121 D A S L V I T D L 3 131 L E D Y G R Y K C 3 133 D Y G R Y K
C E V 3 157 Q G V V F P Y F P 3 176 E A Q Q A C L D Q 3 178 Q Q A C
L D Q D A 3 216 Q Y P I T K P R E 3 241 W D K D K S R Y D 3 248 Y D
V F C F T S N 3 257 F N G R F Y Y L I 3 268 T K L T Y D E A V 3 274
E A V Q A C L N D 3 305 D A G W L A D G S 3 37 G P H L L V E A E 2
60 P C K F Y R D P T 2 81 W T K L T S D Y L 2 96 V S M G Y H K K T
2 127 T D L T L E D Y G 2 137 Y K C E V I E G L 2 173 N F H E A Q Q
A C 2 182 L D Q D A V I A S 2 190 S F D Q L Y D A W 2 198 W R G G L
D W C N 2 210 L S D G S V Q Y P 2 211 S D G S V Q Y P I 2 267 P T K
L T Y D E A 2 271 T Y D E A V Q A C 2 309 L A D G S V R Y P 2 311 D
G S V R Y P I S 2 327 P T E A A V R F V 2 336 G F P D K K H K L 2
339 D K K H K L Y G V 2 19 S D N Y T L D H D 1 21 N Y T L D H D R A
1 71 G S G I H K I R I 1 84 L T S D Y L K E V 1 99 G Y H K K T Y G
G 1 110 G R V F L K G G S 1 160 V F P Y F P R L G 1 185 D A V I A S
F D Q 1 227 G G Q N T V P G V 1 242 D K D K S R Y D V 1 276 V Q A C
L N D G A 1 151P3D4 v.2: HLA Peptide Scoring Results A3 9-mers
SYFPEITHI 34 K V D L L V P T K 28 20 S I R D H S G Q K 27 56 H V Q
F V G S Y K 27 238 T I A P L A A T R 26 88 L L G R K A V V V 25 179
A V T A T L E E K 25 241 P L A A T R A T R 25 385 S L E E G L G G K
25 163 K V C L S G A P H 24 269 A L S A R A P V P 24 373 S G Y C G
A L W K 24 87 V L L G R K A V V 23 183 T L E E K R K E K 23 343 V L
A R G K P Q R 23 389 G L G G K Q K D K 23 37 L L V P T K V T G 21
75 T V Y Q D E K Q R 21 111 K L K Y L A F L H 21 59 F V G S Y K L A
Y 20 86 K V L L G R K A V 20 323 P S G G G G L K K 20 10 P L R A L
H I V V 19 42 K V T G I I T Q G 19 46 I I T Q G A K D F 19 134 Q V
P S R I F W R 19 322 S P S G G G G L K 19 342 N V L A R G K P Q 19
346 R G K P Q R K P K 19 387 E E G L G G K Q K 19 1 M L E H T T K T
F 18 112 L K Y L A F L H K 18 199 N K Q L M R L Q K 18 201 Q L M R
L Q K Q A 18 13 A L H I V V E S I 17 16 I V V E S I R D H 17 22 R D
H S G Q K M K 17 45 G I I T Q G A K D 17 154 Q G H A S E A Y K 17
192 A E I H Y R K N K 17 204 R L Q K Q A E K N 17 207 K Q A E K N M
K K 17 264 A H R P P A L S A 17 306 S L S P Y G P R N 17 332 P A R
H C Q G Q K 17 344 L A R G K P Q R K 17 36 D L L V P T K V T 16 44
T G I I T Q G A K 16 51 A K D F G H V Q F 16 117 F L H K R M N T N
16 203 M R L Q K Q A E K 16 249 R I G H P G G R T 16 340 K H N V L
A R G K 16 369 D L A G S G Y C G 16 84 K D K V L L G R K 15 100 G I
N I S G S F C 15 109 R N K L K Y L A F 15 137 S R I F W R Q E K 15
206 Q K Q A E K N M K 15 226 G G S P R G L G F 15 256 R T P R A G S
S A 15 257 T P R A G S S A H 15 302 S T Y D S L S P Y 15 361 Y V E
N G R P A D 15 378 A L W K A I E S L 15 7 K T F P L R A L H 14 64 K
L A Y S N D G E 14 138 R I F W R Q E K A 14 155 G H A S E A Y K K
14 169 A P H E V G W K Y 14 211 K N M K K K I D K 14 222 E S P G G
G S P R 14 231 G L G F I F K T I 14 250 I G H P G G R T P 14 284 W
L P L R T P W T 14 285 L P L R T P W T R 14 286 P L R T P W T R P
14 296 S C P T S S S T Y 14 315 P L P N P R H S P 14 328 G L K K P
A R H C 14 78 Q D E K Q R K D K 13 93 A V V V S C E G I 13 95 V V S
C E G I N I 13 106 S F C R N K L K Y 13 165 C L S G A P H E V 13
176 K Y Q A V T A T L 13 187 K R K E K A E I H 13 194 I H Y R K N K
Q L 13 216 K I D K Y T E S P 13 228 S P R G L G F I F 13 229 P R G
L G F I F K 13 244 A T R A T R I G H 13 272 A R A P V P A A S 13
275 P V P A A S P A A 13 367 P A D L A G S G Y 13 26 G Q K M K Q D
K K 12 38 L V P T K V T G I 12 69 N D G E H W T V Y 12 83 R K D K V
L L G R 12 103 I S G S F C R N K 12 105 G S F C R N K L K 12 121 R
M N T N P S R R 12 129 R P Y H F Q V P S 12 168 G A P H E V G W K
12 172 E V G W K Y Q A V 12 174 G W K Y Q A V T A 12 190 E K A E I
H Y R K 12 208 Q A E K N M K K K 12 237 K T I A P L A A T 12 273 R
A P V P A A S P 12 274 A P V P A A S P A 12 366 R P A D L A G S G
12 14 L H I V V E S I R 11 17 V V E S I R D H S 11 25 S G Q K M K Q
D K 11 76 V Y Q D E K Q R K 11 89 L G R K A V V V S 11 94 V V V S C
E G I N 11 99 E G I N I S G S F 11 101 I N I S G S F C R 11 113 K Y
L A F L H K R 11 114 Y L A F L H K R M 11 143 Q E K A D G G S C 11
181 T A T L E E K R K 11 196 Y R K N K Q L M R 11 221 T E S P G G G
S P 11 234 F I F K T I A P L 11 248 T R I G H P G G R 11 255 G R T
P R A G S S 11 265 H R P P A L S A R 11 320 R H S P S G G G G 11
327 G G L K K P A R H 11 353 P K S E N N S W Y 11 382 A I E S L E E
G L 11 11 L R A L H I V V E 10 12 R A L H I V V E S 10 73 H W T V Y
Q D E K 10 81 K Q R K D K V L L 10 90 G R K A V V V S C 10 102 N I
S G S F C R N 10 120 K R M N T N P S R 10 123 N T N P S R R P Y 10
125 N P S R R P Y H F 10 127 S R R P Y H F Q V 10 144 E K A D G G S
C C 10 160 A Y K K V C L S G 10 188 R K E K A E I H Y 10 189 K E K
A E I H Y R 10 193 E I H Y R K N K Q 10 246 R A T R I G H P G 10
251 G H P G G R T P R 10 258 P R A G S S A H R 10 283 A W L P L R T
P W 10 330 K K P A R H C Q G 10 333 A R H C Q G Q K H 10 348 K P Q
R K P K S E 10 364 N G R P A D L A G 10 368 A D L A G S G Y C 10
392 G K Q K D K E R K 10 395 K D K E R K A E N 10 8 T F P L R A L H
I 9 19 E S I R D H S G Q 9 50 G A K D F G H V Q 9 55 G H V Q F V G
S Y 9 61 G S Y K L A Y S N 9 65 L A Y S N D G E H 9 91 R K A V V V
S C E 9 157 A S E A Y K K V C 9 167 S G A P H E V G W 9 214 K K K I
D K Y T E 9 215 K K I D K Y T E S 9 247 A T R I G H P G G 9 266 R P
P A L S A R A 9 270 L S A R A P V P A 9 278 A A S P A A W L P 9 295
S S C P T S S S T 9 313 R N P L P N P R H 9 338 G Q K H N V L A R 9
384 E S L E E G L G G 9 399 R K A E N G P H L 9 15 H I V V E S I R
D 8 28 K M K Q D K K V D 8 32 D K K V D L L V P 8 33 K K V D L L V
P T 8 80 E K Q R K D K V L 8 82 Q R K D K V L L G 8 116 A F L H K R
M N T 8 128 R R P Y H F Q V P 8 150 S C C P Q G H A S 8 152 C P Q G
H A S E A 8 212 N M K K K I D K Y 8 230 R G L G F I F K T 8 240 A P
L A A T R A T 8 263 S A H R P P A L S 8 276 V P A A S P A A W 8 277
P A A S P A A W L 8 279 A S P A A W L P L 8 280 S P A A W L P L R 8
282 A A W L P L R T P 8 289 T P W T R P S S C 8 293 R P S S C P T S
S 8 308 S P Y G P R N P L 8 312 P R N P L P N P R 8 316 L P N P R H
S P S 8 362 V E N G R P A D L 8 398 E R K A E N G P H 8 31 Q D K K
V D L L V 7 48 T Q G A K D F G H 7 66 A Y S N D G E H W 7 68 S N D
G E H W T V 7 124 T N P S R R P Y H 7 136 P S R I F W R Q E 7 145 K
A D G G S C C P 7 151 C C P Q G H A S E 7 153 P Q G H A S E A Y 7
158 S E A Y K K V C L 7 164 V C L S G A P H E 7 173 V G W K Y Q A V
T 7 200 K Q L M R L Q K Q 7 239 I A P L A A T R A 7 242 L A A T R A
T R I 7 254 G G R T P R A G S 7 259 R A G S S A H R P 7 271 S A R A
P V P A A 7 288 R T P W T R P S S 7 305 D S L S P Y G P R 7 310 Y G
P R N P L P N 7 318 N P R H S P S G G 7 326 G G G L K K P A R 7 331
K P A R H C Q G Q 7 339 Q K H N V L A R G 7 350 Q R K P K S E N N 7
371 A G S G Y C G A L 7 381 K A I E S L E E G 7 396 D K E R K A E N
G 7 400 K A E N G P H L L 7 29 M K Q D K K V D L 6 35 V D L L V P T
K V 6 41 T K V T G I I T Q 6 62 S Y K L A Y S N D 6 126 P S R R P Y
H F Q 6 130 P Y H F Q V P S R 6 139 I F W R Q E K A D 6 140 F W R Q
E K A D G 6 166 L S G A P H E V G 6 175 W K Y Q A V T A T 6 182 A T
L E E K R K E 6 185 E E K R
K E K A E 6 186 E K R K E K A E I 6 217 I D K Y T E S P G 6 219 K Y
T E S P G G G 6 227 G S P R G L G F I 6 235 I F K T I A P L A 6 236
F K T I A P L A A 6 243 A A T R A T R I G 6 262 S S A H R P P A L 6
267 P P A L S A R A P 6 268 P A L S A R A P V 6 290 P W T R P S S C
P 6 291 W T R P S S C P T 6 301 S S T Y D S L S P 6 314 N P L P N P
R H S 6 321 H S P S G G G G L 6 334 R H C Q G Q K H N 6 337 Q G Q K
H N V L A 6 349 P Q R K P K S E N 6 352 K P K S E N N S W 6 355 S E
N N S W Y V E 6 359 S W Y V E N G R P 6 363 E N G R P A D L A 6 372
G S G Y C G A L W 6 377 G A L W K A I E S 6 379 L W K A I E S L E 6
386 L E E G L G G K Q 6 388 E G L G G K Q K D 6 391 G G K Q K D K E
R 6 393 K Q K D K E R K A 6 397 K E R K A E N G P 6 5 T T K T F P L
R A 5 9 F P L R A L H I V 5 18 V E S I R D H S G 5 21 I R D H S G Q
K M 5 52 K D F G H V Q F V 5 53 D F G H V Q F V G 5 97 S C E G I N
I S G 5 107 F C R N K L K Y L 5 110 N K L K Y L A F L 5 118 L H K R
M N T N P 5 131 Y H F Q V P S R I 5 141 W R Q E K A D G G 5 142 R Q
E K A D G G S 5 146 A D G G S C C P Q 5 148 G G S C C P Q G H 5 159
E A Y K K V C L S 5 162 K K V C L S G A P 5 171 H E V G W K Y Q A 5
177 Y Q A V T A T L E 5 178 Q A V T A T L E E 5 180 V T A T L E E K
R 5 197 R K N K Q L M R L 5 202 L M R L Q K Q A E 5 209 A E K N M K
K K I 5 223 S P G G G S P R G 5 233 G F I F K T I A P 5 253 P G G R
T P R A G 5 281 P A A W L P L R T 5 294 P S S C P T S S S 5 309 P Y
G P R N P L P 5 317 P N P R H S P S G 5 324 S G G G G L K K P 5 329
L K K P A R H C Q 5 336 C Q G Q K H N V L 5 358 N S W Y V E N G R 5
365 G R P A D L A G S 5 376 C G A L W K A I E 5 380 W K A I E S L E
E 5 4 H T T K T F P L R 4 24 H S G Q K M K Q D 4 30 K Q D K K V D L
L 4 40 P T K V T G I I T 4 47 I T Q G A K D F G 4 49 Q G A K D F G
H V 4 54 F G H V Q F V G S 4 58 Q F V G S Y K L A 4 60 V G S Y K L
A Y S 4 63 Y K L A Y S N D G 4 67 Y S N D G E H W T 4 70 D G E H W
T V Y Q 4 85 D K V L L G R K A 4 92 K A V V V S C E G 4 98 C E G I
N I S G S 4 132 H F Q V P S R I F 4 133 F Q V P S R I F W 4 161 Y K
K V C L S G A 4 191 K A E I H Y R K N 4 198 K N K Q L M R L Q 4 218
D K Y T E S P G G 4 220 Y T E S P G G G S 4 245 T R A T R I G H P 4
252 H P G G R T P R A 4 292 T R P S S C P T S 4 300 S S S T Y D S L
S 4 311 G P R N P L P N P 4 351 R K P K S E N N S 4 354 K S E N N S
W Y V 4 356 E N N S W Y V E N 4 360 W Y V E N G R P A 4 383 I E S L
E E G L G 4 394 Q K D K E R K A E 4 23 D H S G Q K M K Q 3 71 G E H
W T V Y Q D 3 79 D E K Q R K D K V 3 96 V S C E G I N I S 3 119 H K
R M N T N P S 3 135 V P S R I F W R Q 3 147 D G G S C C P Q G 3 195
H Y R K N K Q L M 3 224 P G G G S P R G L 3 260 A G S S A H R P P 3
261 G S S A H R P P A 3 287 L R T P W T R P S 3 307 L S P Y G P R N
P 3 341 H N V L A R G K P 3 345 A R G K P Q R K P 3 375 Y C G A L W
K A I 3 27 Q K M K Q D K K V 2 39 V P T K V T G I I 2 57 V Q F V G
S Y K L 2 77 Y Q D E K Q R K D 2 104 S G S F C R N K L 2 115 L A F
L H K R M N 2 170 P H E V G W K Y Q 2 184 L E E K R K E K A 2 225 G
G G S P R G L G 2 232 L G F I F K T I A 2 299 T S S S T Y D S L 2
304 Y D S L S P Y G P 2 325 G G G G L K K P A 2 335 H C Q G Q K H N
V 2 347 G K P Q R K P K S 2 370 L A G S G Y C G A 2 374 G Y C G A L
W K A 2 2 L E H T T K T F P 1 3 E H T T K T F P L 1 6 T K T F P L R
A L 1 43 V T G I I T Q G A 1 72 E H W T V Y Q D E 1 122 M N T N P S
R R P 1 149 G S C C P Q G H A 1 156 H A S E A Y K K V 1 205 L Q K Q
A E K N M 1 210 E K N M K K K I D 1 213 M K K K I D K Y T 1 297 C P
T S S S T Y D 1 319 P R H S P S G G G 1
[0827]
34TABLE XXVII SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:
HLA Peptide Scoring Results A26 9-mers SYFPEITHI 155 D L Q G V V F
P Y 30 249 D V F C F T S N F 30 159 V V F P Y F P R L 28 129 L T L
E D Y G R Y 27 230 N T V P G V R N Y 27 186 A V I A S F D Q L 26
126 I T D L T L E D Y 25 140 E V I E G L E D D 24 148 D T V V V A L
D L 24 91 E V D V F V S M G 23 93 D V F V S M G Y H 23 183 D Q D A
V I A S F 23 187 V I A S F D Q L Y 23 285 Q I A K V G Q I F 23 329
E A A V R F V G F 23 264 L I H P T K L T Y 22 308 W L A D G S V R Y
22 87 D Y L K E V D V F 21 146 E D D T V V V A L 21 153 A L D L Q G
V V F 21 209 W L S D G S V Q Y 21 253 F T S N F N G R F 21 56 N V T
L P C K F Y 20 76 K I R I K W T K L 20 256 N F N G R F Y Y L 20 291
Q I F A A W K I L 20 81 W T K L T S D Y L 19 162 P Y F P R L G R Y
19 166 R L G R Y N L N F 19 103 K T Y G G Y Q G R 18 121 D A S L V
I T D L 18 336 G F P D K K H K L 18 62 K F Y R D P T A F 17 100 Y H
K K T Y G G Y 17 151 V V A L D L Q G V 17 288 K V G Q I F A A W 17
293 F A A W K I L G Y 17 84 L T S D Y L K E V 16 123 S L V I T D L
T L 16 124 L V I T D L T L E 16 243 K D K S R Y D V F 16 267 P T K
L T Y D E A 16 313 S V R Y P I S R P 16 340 K K H K L Y G V Y 16 7
L V L I S I C W A 15 16 D H L S D N Y T L 15 58 T L P C K F Y R D
15 90 K E V D V F V S M 15 95 F V S M G Y H K K 15 128 D L T L E D
Y G R 15 137 Y K C E V I E G L 15 156 L Q G V V F P Y F 15 214 S V
Q Y P I T K P 15 345 Y G V Y C F R A Y 15 5 L L L V L I S I C 14 42
V E A E Q A K V F 14 45 E Q A K V F S H R 14 48 K V F S H R G G N
14 83 K L T S D Y L K E 14 111 R V F L K G G S D 14 149 T V V V A L
D L Q 14 158 G V V F P Y F P R 14 190 S F D Q L Y D A W 14 219 I T
K P R E P C G 14 240 F W D K D K S R Y 14 245 K S R Y D V F C F 14
275 A V Q A C L N D G 14 326 S P T E A A V R F 14 327 P T E A A V R
F V 14 342 H K L Y G V Y C F 14 343 K L Y G V Y C F R 14 1 M K S L
L L L V L 13 3 S L L L L V L I S 13 4 L L L L V L I S I 13 14 W A D
H L S D N Y 13 17 H L S D N Y T L D 13 27 D R A I H I Q A E 13 32 I
Q A E N G P H L 13 80 K W T K L T S D Y 13 119 D S D A S L V I T 13
125 V I T D L T L E D 13 141 V I E G L E D D T 13 231 T V P G V R N
Y G 13 270 L T Y D E A V Q A 13 337 F P D K K H K L Y 13 339 D K K
H K L Y G V 13 8 V L I S I C W A D 12 22 Y T L D H D R A I 12 29 A
I H I Q A E N G 12 35 E N G P H L L V E 12 40 L L V E A E Q A K 12
41 L V E A E Q A K V 12 55 G N V T L P C K F 12 57 V T L P C K F Y
R 12 69 A F G S G I H K I 12 73 G I H K I R I K W 12 88 Y L K E V D
V F V 12 92 V D V F V S M G Y 12 113 F L K G G S D S D 12 116 G G S
D S D A S L 12 132 E D Y G R Y K C E 12 150 V V V A L D L Q G 12
212 D G S V Q Y P I T 12 252 C F T S N F N G R 12 255 S N F N G R F
Y Y 12 297 K I L G Y D R C D 12 9 L I S I C W A D H 11 10 I S I C W
A D H L 11 25 D H D R A I H I Q 11 51 S H R G G N V T L 11 67 P T A
F G S G I H 11 78 R I K W T K L T S 11 105 Y G G Y Q G R V F 11 147
D D T V V V A L D 11 181 C L D Q D A V I A 11 201 G L D W C N A G W
11 218 P I T K P R E P C 11 232 V P G V R N Y G F 11 260 R F Y Y L
I H P T 11 311 D G S V R Y P I S 11 317 P I S R P R R R C 11 334 F
V G F P D K K H 11 346 G V Y C F R A Y N 11 11 S I C W A D H L S 10
23 T L D H D R A I H 10 31 H I Q A E N G P H 10 97 S M G Y H K K T
Y 10 106 G G Y Q G R V F L 10 144 G L E D D T V V V 10 171 N L N F
H E A Q Q 10 173 N F H E A Q Q A C 10 174 F H E A Q Q A C L 10 193
Q L Y D A W R G G 10 194 L Y D A W R G G L 10 234 G V R N Y G F W D
10 254 T S N F N G R F Y 10 263 Y L I H P T K L T 10 279 C L N D G
A Q I A 10 331 A V R F V G F P D 10 39 H L L V E A E Q A 9 130 T L
E D Y G R Y K 9 164 F P R L G R Y N L 9 210 L S D G S V Q Y P 9 239
G F W D K D K S R 9 242 D K D K S R Y D V 9 262 Y Y L I H P T K L 9
269 K L T Y D E A V Q 9 271 T Y D E A V Q A C 9 272 Y D E A V Q A C
L 9 333 R F V G F P D K K 9 6 L L V L I S I C W 8 33 Q A E N G P H
L L 8 36 N G P H L L V E A 8 43 E A E Q A K V F S 8 66 D P T A F G
S G I 8 94 V F V S M G Y H K 8 112 V F L K G G S D S 8 143 E G L E
D D T V V 8 163 Y F P R L G R Y N 8 189 A S F D Q L Y D A 8 202 L D
W C N A G W L 8 205 C N A G W L S D G 8 224 E P C G G Q N T V 8 273
D E A V Q A C L N 8 274 E A V Q A C L N D 8 282 D G A Q I A K V G 8
284 A Q I A K V G Q I 8 287 A K V G Q I F A A 8 298 I L G Y D R C D
A 8 301 Y D R C D A G W L 8 304 C D A G W L A D G 8 305 D A G W L A
D G S 8 309 L A D G S V R Y P 8 13 C W A D H L S D N 7 20 D N Y T L
D H D R 7 49 V F S H R G G N V 7 72 S G I H K I R I K 7 120 S D A S
L V I T D 7 133 D Y G R Y K C E V 7 145 L E D D T V V V A 7 160 V F
P Y F P R L G 7 176 E A Q Q A C L D Q 7 192 D Q L Y D A W R G 7 244
D K S R Y D V F C 7 259 G R F Y Y L I H P 7 281 N D G A Q I A K V 7
292 I F A A W K I L G 7 296 W K I L G Y D R C 7 302 D R C D A G W L
A 7 332 V R F V G F P D K 7 2 K S L L L L V L I 6 37 G P H L L V E
A E 6 44 A E Q A K V F S H 6 52 H R G G N V T L P 6 65 R D P T A F
G S G 6 68 T A F G S G I H K 6 79 I K W T K L T S D 6 107 G Y Q G R
V F L K 6 136 R Y K C E V I E G 6 154 L D L Q G V V F P 6 165 P R L
G R Y N L N 6 182 L D Q D A V I A S 6 185 D A V I A S F D Q 6 196 D
A W R G G L D W 6 197 A W R G G L D W C 6 203 D W C N A G W L S 6
227 G G Q N T V P G V 6 250 V F C F T S N F N 6 265 I H P T K L T Y
D 6 19 S D N Y T L D H D 5 54 G G N V T L P C K 5 59 L P C K F Y R
D P 5 74 I H K I R I K W T 5 108 Y Q G R V F L K G 5 109 Q G R V F
L K G G 5 169 R Y N L N F H E A 5 177 A Q Q A C L D Q D 5 246 S R Y
D V F C F T 5 248 Y D V F C F T S N 5 294 A A W K I L G Y D 5 335 V
G F P D K K H K 5 28 R A I H I Q A E N 4 30 I H I Q A E N G P 4 64
Y R D P T A F G S 4 89 L K E V D V F V S 4 114 L K G G S D S D A 4
167 L G R Y N L N F H 4 172 L N F H E A Q Q A 4 217 Y P I T K P R E
P 4 233 P G V R N Y G F W 4 235 V R N Y G F W D K 4 251 F C F T S N
F N G 4 257 F N G R F Y Y L I 4 258 N G R F Y Y L I H 4 280 L N D G
A Q I A K 4 315 R Y P I S R P R R 4 316 Y P I S R P R R R 4 324 R C
S P T E A A V 4 330 A A V R F V G F P 4 61 C K F Y R D P T A 3 77 I
R I K W T K L T 3 96 V S M G Y H K K T 3 99 G Y H K K T Y G G 3 104
T Y G G Y Q G R V 3 117 G S D S D A S L V 3 175 H E A Q Q A C L D 3
178 Q Q A C L D Q D A 3 180 A C L D Q D A V I 3 198 W R G G L D W C
N 3 216 Q Y P I T K P R E 3 221 K P R E P C G G Q 3 222 P R E P C G
G Q N 3 223 R E P C G G Q N T 3 225 P C G G Q N T V P 3 236 R N Y G
F W D K D 3 238 Y G F W D K D K S 3 241 W D K D K S R Y D 3 276 V Q
A C L N D G A 3 290 G Q I F A A W K I 3 300 G Y D R C D A G W 3 24
L D H D R A I H I 2 34 A E N G P H L L V 2 38 P H L L V E A E Q 2
46 Q A K V F S H R G 2 47 A K V F S H R G G 2 63 F Y R D P T A F G
2 70 F G S G I H K I R 2 75 H K I R I K W T K 2 85 T S D Y L K E V
D 2 86 S D Y L K E V D V 2 110 G R V F L K G G S 2 115 K G G S D S
D A S 2 131 L E D Y G R Y K C 2 135 G R Y K C E V I E 2 152 V A L D
L Q G V V 2 168 G R Y N L N F H E 2 184 Q D A V I A S F D 2 200 G G
L D W C N A G 2 206 N A G W L S D G S 2 207 A G W L S D G S V 2 208
G W L S D G S V Q 2 215 V Q Y P I T K P R 2 220 T K P R E P C G G 2
226 C G G Q N T V P G 2 229 Q N T V P G V R N 2 266 H P T K L T Y D
E 2 278 A C L N D G A Q I 2 283 G A Q I A K V G Q 2 295 A W K I L G
Y D R 2 299 L G Y D R C D A G 2 303 R C D A G W L A D 2 314 V R Y P
I S R P R 2 318 I S R P R R R C S 2 319 S R P R R R C S P 2 322 R R
R C S P T E A 2 323 R R C S P T E A A 2 325 C S P T E A A V R 2 338
P D K K H K L Y G 2 341 K H K L Y G V Y C 2 12 I C W A D H L S D 1
15 A D H L S D N Y T 1 18 L S D N Y T L D H 1 21 N Y T L D H D R A
1 26 H D R A I H I Q A 1 60 P C K F Y R D P T 1 71 G S G I H K I R
I 1 82 T K L T S D Y L K 1 98 M G Y H K K T Y G 1 101 H K K T Y G G
Y Q 1 102 K K T Y G G Y Q G 1 118 S D S D A S L V I 1 127 T D L T L
E D Y G 1 134 Y G R Y K C E V I 1 139 C E V I E G L E D 1 161 F P Y
F P R L G R 1 170 Y N L N F H E A Q 1 179 Q A C L D Q D A V 1 191 F
D Q L Y D A W R 1 195 Y D A W R G G L D 1 199 R G G L D W C N A 1
204 W C N A G W L S D 1 211 S D G S V Q Y P I 1 213 G S V Q Y P I T
K 1 247 R Y D V F C F T S 1 261 F Y Y L I H P T K 1 268 T K L T Y D
E A V 1 277 Q A C L N D G A Q 1 286 I A K V G Q I F A 1 289 V G Q I
F A A W K 1 306 A G W L A D G S V 1 307 G W L A D G S V R 1 310 A D
G S V R Y P I 1 312 G S V R Y P I S R 1 320 R P R R R C S P T 1 321
P R R R C S P T E 1 328 T E A A V R F V G 1 344 L Y G V Y C F R A 1
151P3D4 v.2: HLA Peptide Scoring Results A26 9-mers SYFPEITHI 302 S
T Y D S L S P Y 27 234 F I F K T I A P L 26 123 N T N P S R R P Y
23 172 E V G W K Y Q A V 23 59 F V G S Y K L A Y 22 378 A L W K A I
E S L 22 46 I I T Q G A K D F 21 382 A I E S L E E G L 21 99 E G I
N I S G S F 19 114 Y L A F L H K R M 19 1 M L E H T T K T F 18 102
N I S G S F C R N 18 212 N M K K K I D K Y 18 237 K T I A P L A A T
18 369 D L A G S G Y C G 18 16 I V V E S I R D H 17 34 K V D L L V
P T K 17 38 L V P T K V T G I 17 42 K V T G I I T Q G 17 106 S F C
R N K L K Y 17 109 R N K L K Y L A F 17 193 E I H Y R K N K Q 17 4
H T T K T F P L R 16 7 K T F P L R A L H 16 55 G H V Q F V G S Y 16
132 H F Q V P S R I F 16 134 Q V P S R I F W R 16 197 R K N K Q L M
R L 16 3 E H T T K T F P L 15 30 K Q D K K V D L L 15 45 G I I T Q
G A K D 15 80 E K Q R K D K V L 15 179 A V T A T L E E K 15 238 T I
A P L A A T R 15 385 S L E E G L G G K 15 36 D L L V P T K V T 14
110 N K L K Y L A F L 14 299 T S S S T Y D S L 14 6 T K T F P L R A
L 13 13 A L H I V V E S I 13 51 A K D F G H V Q F 13 58 Q F V G S Y
K L A 13 107 F C R N K L K Y L 13 117 F L H K R M N T N 13 138 R I
F W R Q E K A 13 169 A P H E V G W K Y 13 180 V T A T L E E K R 13
182 A T L E E K R K E 13 216 K I D K Y T E S P 13 226 G G S P R G L
G F 13 228 S P R G L G F I F 13 256 R T P R A G S S A 13 275 P V P
A A S P A A 13 288 R T P W T R P S S 13 291 W T R P S S C P T 13
296 S C P T S S S T Y 13 353 P K S E N N S W Y 13 356 E N N S W Y V
E N 13 367 P A D L A G S G Y 13 399 R K A E N G P H L 13 5 T T K T
F P L R A 12 17 V V E S I R D H S 12 20 S I R D H S G Q K 12 21 I R
D H S G Q K M 12 43 V T G I I T Q G A 12 47 I T Q G A K D F G 12 53
D F G H V Q F V G 12 69 N D G E H W T V Y 12 74 W T V Y Q D E K Q
12 75 T V Y Q D E K Q R 12 93 A V V V S C E G I 12 100 G I N I S G
S F C 12 159 E A Y K K V C L S 12 163 K V C L S G A P H 12 183 T L
E E K R K E K 12 188 R K E K A E I H Y 12 220 Y T E S P G G G S 12
224 P G G G S P R G L 12 231 G L G F I F K T I 12 247 A T R I G H P
G G 12 298 P T S S S T Y D S 12 306 S L S P Y G P R N 12 361 Y V E
N G R P A D 12 15 H I V V E S I R D 11 23 D H S G Q K M K Q 11 29 M
K Q D K K V D L 11 32 D K K V D L L V P 11 37 L L V P T K V T G 11
40 P T K V T G I I T 11 56 H V Q F V G S Y K 11 57 V Q F V G S Y K
L 11 64 K L A Y S N D G E 11 72 E H W T V Y Q D E 11 86 K V L L G R
K A V 11 87 V L L G R K A V V 11 94 V V V S C E G I N 11 95 V V S C
E G I N I 11 125 N P S R R P Y H F 11 153 P Q G H A S E A Y 11 158
S E A Y K K V C L 11 165 C L S G A P H E V 11 204 R L Q K Q A E K N
11 205 L Q K Q A E K N M 11 244 A T R A T R I G H 11 249 R I G H P
G G R T 11 262 S S A H R P P A L 11 277 P A A S P A A W L 11 305 D
S L S P Y G P R 11 321 H S P S G G G G L 11 328 G L K K P A R H C
11 343 V L A R G K P Q R 11 362 V E N G R P A D L 11 371 A G S G Y
C G A L 11 389 G L G G K Q K D K 11 19 E S I R D H S G Q 10 81 K Q
R K D K V L L 10 88 L L G R K A V V V 10 111 K L K Y L A F L H 10
190 E K A E I H Y R K 10 194 I H Y R K N K Q L 10 195 H Y R K N K Q
L M 10 201 Q L M R L Q K Q A 10 222 E S P G G G S P R 10 233 G F I
F K T I A P 10 241 P L A A T R A T R 10 284 W L P L R T P W T 10
308 S P Y G P R N P L 10 315 P L P N P R H S P 10 336 C Q G Q K H N
V L 10 342 N V L A R G K P Q 10 381 K A I E S L E E G 10 388 E G L
G G K Q K D 10 10 P L R A L H I V V 9 52 K D F G H V Q F V 9 79 D E
K Q R K D K V 9 104 S G S F C R N K L 9 116 A F L H K R M N T 9 144
E K A D G G S C C 9 147 D G G S C C P Q G 9 176 K Y Q A V T A T L 9
185 E E K R K E K A E 9 186 E K R K E K A E I 9 215 K K I D K Y T E
S 9 265 H R P P A L S A R 9 269 A L S A R A P V P 9 279 A S P A A W
L P L 9 286 P L R T P W T R P 9 384 E S L E E G L G G 9 8 T F P L R
A L H I 8 85 D K V L L G R K A 8 139 I F W R Q E K A D 8 218 D K Y
T E S P G G 8 235 I F K T I A P L A 8 396 D K E R K A E N G 8 400 K
A E N G P H L L 8 24 H S G Q K M K Q D 7 33 K K V D L L V P T 7 49
Q G A K D F G H V 7 54 F G H V Q F V G S 7 62 S Y K L A Y S N D 7
70 D G E H W T V Y Q 7 82 Q R K D K V L L G 7 83 R K D K V L L G R
7 84 K D K V L L G R K 7 90 G R K A V V V S C 7 130 P Y H F Q V P S
R 7 156 H A S E A Y K K V 7 161 Y K K V C L S G A 7 198 K N K Q L M
R L Q 7 210 E K N M K K K I D 7 230 R G L G F I F K T 7 324 S G G G
G L K K P 7 365 G R P A D L A G S 7 374 G Y C G A L W K A 7 387 E E
G L G G K Q K 7 398 E R K A E N G P H 7 11 L R A L H I V V E 6 12 R
A L H I V V E S 6 60 V G S Y K L A Y S 6 89 L G R K A V V V S 6 91
R K A V V V S C E 6 96 V S C E G I N I S 6 98 C E G I N I S G S 6
128 R R P Y H F Q V P 6 175 W K Y Q A V T A T 6 200 K Q L M R L Q K
Q 6 207 K Q A E K N M K K 6 208 Q A E K N M K K K 6 245 T R A T R I
G H P 6 258 P R A G S S A H R 6 271 S A R A P V P A A 6 280 S P A A
W L P L R 6 311 G P R N P L P N P 6 338 G Q K H N V L A R 6 339 Q K
H N V L A R G 6 363 E N G R P A D L A 6 370 L A G S G Y C G A 6 71
G E H W T V Y Q D 5 77 Y Q D E K Q R K D 5 112 L K Y L A F L H K 5
113 K Y L A F L H K R 5 131 Y H F Q V P S R I 5 135 V P S R I F W R
Q 5 167 S G A P H E V G W 5 168 G A P H E V G W K 5 189 K E K A E I
H Y R 5 191 K A E I H Y R K N 5 227 G S P R G L G F I 5 248 T R I G
H P G G R 5 272 A R A P V P A A S 5 344 L A R G K P Q R K 5 350 Q R
K P K S E N N 5 357 N N S W Y V E N G 5 395 K D K E R K A E N 5 9 F
P L R A L H I V 4 41 T K V T G I I T Q 4 126 P S R R P Y H F Q 4
137 S R I F W R Q E K 4 141 W R Q E K A D G G 4 150 S C C P Q G H A
S 4 151 C C P Q G H A S E 4 152 C P Q G H A S E A 4 187 K R K E K A
E I H 4 203 M R L Q K Q A E K 4 219 K Y T E S P G G G 4 223 S P G G
G S P R G 4 229 P R G L G F I F K 4 252 H P G G R T P R A 4 266 R P
P A L S A R A 4 276 V P A A S P A A W 4 282 A A W L P L R T P 4 292
T R P S S C P T S 4 295 S S C P T S S S T 4 303 T Y D S L S P Y G 4
320 R H S P S G G G G 4 327 G G L K K P A R H 4 335 H C Q G Q K H N
V 4 346 R G K P Q R K P K 4 347 G K P Q R K P K S 4 351 R K P K S E
N N S 4 366 R P A D L A G S G 4 386 L E E G L G G K Q 4 391 G G K Q
K D K E R 4 393 K Q K D K E R K A 4 14 L H I V V E S I R 3 26 G Q K
M K Q D K K 3 27 Q K M K Q D K K V 3 44 T G I I
T Q G A K 3 61 G S Y K L A Y S N 3 68 S N D G E H W T V 3 76 V Y Q
D E K Q R K 3 97 S C E G I N I S G 3 101 I N I S G S F C R 3 115 L
A F L H K R M N 3 124 T N P S R R P Y H 3 127 S R R P Y H F Q V 3
133 F Q V P S R I F W 3 145 K A D G G S C C P 3 146 A D G G S C C P
Q 3 155 G H A S E A Y K K 3 160 A Y K K V C L S G 3 164 V C L S G A
P H E 3 171 H E V G W K Y Q A 3 174 G W K Y Q A V T A 3 192 A E I H
Y R K N K 3 196 Y R K N K Q L M R 3 202 L M R L Q K Q A E 3 221 T E
S P G G G S P 3 251 G H P G G R T P R 3 255 G R T P R A G S S 3 259
R A G S S A H R P 3 264 A H R P P A L S A 3 267 P P A L S A R A P 3
273 R A P V P A A S P 3 274 A P V P A A S P A 3 281 P A A W L P L R
T 3 283 A W L P L R T P W 3 309 P Y G P R N P L P 3 312 P R N P L P
N P R 3 313 R N P L P N P R H 3 314 N P L P N P R H S 3 316 L P N P
R H S P S 3 317 P N P R H S P S G 3 318 N P R H S P S G G 3 323 P S
G G G G L K K 3 325 G G G G L K K P A 3 326 G G G L K K P A R 3 329
L K K P A R H C Q 3 331 K P A R H C Q G Q 3 333 A R H C Q G Q K H 3
349 P Q R K P K S E N 3 352 K P K S E N N S W 3 364 N G R P A D L A
G 3 390 L G G K Q K D K E 3 394 Q K D K E R K A E 3 22 R D H S G Q
K M K 2 25 S G Q K M K Q D K 2 28 K M K Q D K K V D 2 31 Q D K K V
D L L V 2 48 T Q G A K D F G H 2 50 G A K D F G H V Q 2 65 L A Y S
N D G E H 2 78 Q D E K Q R K D K 2 103 I S G S F C R N K 2 105 G S
F C R N K L K 2 108 C R N K L K Y L A 2 118 L H K R M N T N P 2 120
K R M N T N P S R 2 121 R M N T N P S R R 2 140 F W R Q E K A D G 2
142 R Q E K A D G G S 2 143 Q E K A D G G S C 2 148 G G S C C P Q G
H 2 154 Q G H A S E A Y K 2 162 K K V C L S G A P 2 173 V G W K Y Q
A V T 2 184 L E E K R K E K A 2 209 A E K N M K K K I 2 211 K N M K
K K I D K 2 213 M K K K I D K Y T 2 217 I D K Y T E S P G 2 232 L G
F I F K T I A 2 239 I A P L A A T R A 2 242 L A A T R A T R I 2 250
I G H P G G R T P 2 254 G G R T P R A G S 2 257 T P R A G S S A H 2
268 P A L S A R A P V 2 270 L S A R A P V P A 2 278 A A S P A A W L
P 2 287 L R T P W T R P S 2 289 T P W T R P S S C 2 293 R P S S C P
T S S 2 294 P S S C P T S S S 2 297 C P T S S S T Y D 2 304 Y D S L
S P Y G P 2 307 L S P Y G P R N P 2 319 P R H S P S G G G 2 322 S P
S G G G G L K 2 330 K K P A R H C Q G 2 334 R H C Q G Q K H N 2 337
Q G Q K H N V L A 2 340 K H N V L A R G K 2 345 A R G K P Q R K P 2
348 K P Q R K P K S E 2 360 W Y V E N G R P A 2 375 Y C G A L W K A
I 2 376 C G A L W K A I E 2 377 G A L W K A I E S 2 379 L W K A I E
S L E 2 380 W K A I E S L E E 2 392 G K Q K D K E R K 2 397 K E R K
A E N G P 2 18 V E S I R D H S G 1 35 V D L L V P T K V 1 39 V P T
K V T G I I 1 66 A Y S N D G E H W 1 67 Y S N D G E H W T 1 73 H W
T V Y Q D E K 1 92 K A V V V S C E G 1 122 M N T N P S R R P 1 129
R P Y H F Q V P S 1 136 P S R I F W R Q E 1 149 G S C C P Q G H A 1
177 Y Q A V T A T L E 1 178 Q A V T A T L E E 1 181 T A T L E E K R
K 1 199 N K Q L M R L Q K 1 206 Q K Q A E K N M K 1 214 K K K I D K
Y T E 1 225 G G G S P R G L G 1 236 F K T I A P L A A 1 240 A P L A
A T R A T 1 253 P G G R T P R A G 1 260 A G S S A H R P P 1 261 G S
S A H R P P A 1 263 S A H R P P A L S 1 290 P W T R P S S C P 1 300
S S S T Y D S L S 1 301 S S T Y D S L S P 1 310 Y G P R N P L P N 1
332 P A R H C Q G Q K 1 341 H N V L A R G K P 1 355 S E N N S W Y V
E 1 358 N S W Y V E N G R 1 359 S W Y V E N G R P 1 372 G S G Y C G
A L W 1
[0828]
35TABLE XXVIII SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:
HLA Peptide Scoring Results B*0702 9-mers SYFPEITHI 164 F P R L G R
Y N L 23 320 R P R R R C S P T 20 224 E P C G G Q N T V 19 66 D P T
A F G S G I 18 326 S P T E A A V R F 18 232 V P G V R N Y G F 17 51
S H R G G N V T L 16 146 E D D T V V V A L 16 161 F P Y F P R L G R
16 221 K P R E P C G G Q 16 1 M K S L L L L V L 15 34 A E N G P H L
L V 15 32 I Q A E N G P H L 14 76 K I R I K W T K L 14 106 G G Y Q
G R V F L 14 186 A V I A S F D Q L 14 116 G G S D S D A S L 13 121
D A S L V I T D L 13 153 A L D L Q G V V F 13 159 V V F P Y F P R L
13 194 L Y D A W R G G L 13 256 N F N G R F Y Y L 13 37 G P H L L V
E A E 12 123 S L V I T D L T L 12 148 D T V V V A L D L 12 174 F H
E A Q Q A C L 12 266 H P T K L T Y D E 12 272 Y D E A V Q A C L 12
301 Y D R C D A G W L 12 323 R R C S P T E A A 12 324 R C S P T E A
A V 12 337 F P D K K H K L Y 12 10 I S I C W A D H L 11 59 L P C K
F Y R D P 11 118 S D S D A S L V I 11 145 L E D D T V V V A 11 262
Y Y L I H P T K L 11 287 A K V G Q I F A A 11 291 Q I F A A W K I L
11 310 A D G S V R Y P I 11 329 E A A V R F V G F 11 16 D H L S D N
Y T L 10 33 Q A E N G P H L L 10 81 W T K L T S D Y L 10 90 K E V D
V F V S M 10 119 D S D A S L V I T 10 137 Y K C E V I E G L 10 144
G L E D D T V V V 10 166 R L G R Y N L N F 10 180 A C L D Q D A V I
10 202 L D W C N A G W L 10 217 Y P I T K P R E P 10 245 K S R Y D
V F C F 10 263 Y L I H P T K L T 10 278 A C L N D G A Q I 10 284 A
Q I A K V G Q I 10 316 Y P I S R P R R R 10 322 R R R C S P T E A
10 336 G F P D K K H K L 10 2 K S L L L L V L I 9 26 H D R A I H I
Q A 9 49 V F S H R G G N V 9 62 K F Y R D P T A F 9 69 A F G S G I
H K I 9 77 I R I K W T K L T 9 87 D Y L K E V D V F 9 88 Y L K E V
D V F V 9 96 V S M G Y H K K T 9 104 T Y G G Y Q G R V 9 105 Y G G
Y Q G R V F 9 114 L K G G S D S D A 9 122 A S L V I T D L T 9 134 Y
G R Y K C E V I 9 143 E G L E D D T V V 9 156 L Q G V V F P Y F 9
181 C L D Q D A V I A 9 183 D Q D A V I A S F 9 212 D G S V Q Y P I
T 9 242 D K D K S R Y D V 9 281 N D G A Q I A K V 9 285 Q I A K V G
Q I F 9 298 I L G Y D R C D A 9 327 P T E A A V R F V 9 15 A D H L
S D N Y T 8 36 N G P H L L V E A 8 41 L V E A E Q A K V 8 42 V E A
E Q A K V F 8 50 F S H R G G N V T 8 60 P C K F Y R D P T 8 63 F Y
R D P T A F G 8 84 L T S D Y L K E V 8 86 S D Y L K E V D V 8 141 V
I E G L E D D T 8 142 I E G L E D D T V 8 169 R Y N L N F H E A 8
189 A S F D Q L Y D A 8 199 R G G L D W C N A 8 207 A G W L S D G S
V 8 211 S D G S V Q Y P I 8 223 R E P C G G Q N T 8 227 G G Q N T V
P G V 8 243 K D K S R Y D V F 8 246 S R Y D V F C F T 8 253 F T S N
F N G R F 8 260 R F Y Y L I H P T 8 270 L T Y D E A V Q A 8 286 I A
K V G Q I F A 8 306 A G W L A D G S V 8 22 Y T L D H D R A I 7 61 C
K F Y R D P T A 7 71 G S G I H K I R I 7 74 I H K I R I K W T 7 117
G S D S D A S L V 7 133 D Y G R Y K C E V 7 151 V V A L D L Q G V 7
152 V A L D L Q G V V 7 178 Q Q A C L D Q D A 7 179 Q A C L D Q D A
V 7 249 D V F C F T S N F 7 257 F N G R F Y Y L I 7 268 T K L T Y D
E A V 7 276 V Q A C L N D G A 7 302 D R C D A G W L A 7 342 H K L Y
G V Y C F 7 344 L Y G V Y C F R A 7 4 L L L L V L I S I 6 7 L V L I
S I C W A 6 21 N Y T L D H D R A 6 24 L D H D R A I H I 6 35 E N G
P H L L V E 6 39 H L L V E A E Q A 6 53 R G G N V T L P C 6 55 G N
V T L P C K F 6 172 L N F H E A Q Q A 6 197 A W R G G L D W C 6 218
P I T K P R E P C 6 229 Q N T V P G V R N 6 267 P T K L T Y D E A 6
279 C L N D G A Q I A 6 290 G Q I F A A W K I 6 303 R C D A G W L A
D 6 317 P I S R P R R R C 6 331 A V R F V G F P D 6 339 D K K H K L
Y G V 6 52 H R G G N V T L P 5 188 I A S F D Q L Y D 5 225 P C G G
Q N T V P 5 226 C G G Q N T V P G 5 244 D K S R Y D V F C 5 288 K V
G Q I F A A W 5 313 S V R Y P I S R P 5 318 I S R P R R R C S 5 12
I C W A D H L S D 4 18 L S D N Y T L D H 4 43 E A E Q A K V F S 4
44 A E Q A K V F S H 4 45 E Q A K V F S H R 4 56 N V T L P C K F Y
4 70 F G S G I H K I R 4 108 Y Q G R V F L K G 4 154 L D L Q G V V
F P 4 155 D L Q G V V F P Y 4 158 G V V F P Y F P R 4 209 W L S D G
S V Q Y 4 210 L S D G S V Q Y P 4 214 S V Q Y P I T K P 4 258 N G R
F Y Y L I H 4 280 L N D G A Q I A K 4 304 C D A G W L A D G 4 309 L
A D G S V R Y P 4 328 T E A A V R F V G 4 330 A A V R F V G F P 4
334 F V G F P D K K H 4 341 K H K L Y G V Y C 4 343 K L Y G V Y C F
R 4 3 S L L L L V L I S 3 9 L I S I C W A D H 3 17 H L S D N Y T L
D 3 23 T L D H D R A I H 3 68 T A F G S G I H K 3 78 R I K W T K L
T S 3 80 K W T K L T S D Y 3 83 K L T S D Y L K E 3 91 E V D V F V
S M G 3 103 K T Y G G Y Q G R 3 107 G Y Q G R V F L K 3 115 K G G S
D S D A S 3 125 V I T D L T L E D 3 132 E D Y G R Y K C E 3 135 G R
Y K C E V I E 3 139 C E V I E G L E D 3 150 V V V A L D L Q G 3 167
L G R Y N L N F H 3 176 E A Q Q A C L D Q 3 177 A Q Q A C L D Q D 3
196 D A W R G G L D W 3 198 W R G G L D W C N 3 204 W C N A G W L S
D 3 205 C N A G W L S D G 3 215 V Q Y P I T K P R 3 219 I T K P R E
P C G 3 231 T V P G V R N Y G 3 234 G V R N Y G F W D 3 236 R N Y G
F W D K D 3 264 L I H P T K L T Y 3 269 K L T Y D E A V Q 3 271 T Y
D E A V Q A C 3 274 E A V Q A C L N D 3 275 A V Q A C L N D G 3 292
I F A A W K I L G 3 293 F A A W K I L G Y 3 294 A A W K I L G Y D 3
295 A W K I L G Y D R 3 297 K I L G Y D R C D 3 307 G W L A D G S V
R 3 308 W L A D G S V R Y 3 311 D G S V R Y P I S 3 315 R Y P I S R
P R R 3 321 P R R R C S P T E 3 333 R F V G F P D K K 3 338 P D K K
H K L Y G 3 340 K K H K L Y G V Y 3 27 D R A I H I Q A E 2 28 R A I
H I Q A E N 2 29 A I H I Q A E N G 2 31 H I Q A E N G P H 2 47 A K
V F S H R G G 2 48 K V F S H R G G N 2 64 Y R D P T A F G S 2 65 R
D P T A F G S G 2 73 G I H K I R I K W 2 79 I K W T K L T S D 2 85
T S D Y L K E V D 2 89 L K E V D V F V S 2 95 F V S M G Y H K K 2
99 G Y H K K T Y G G 2 102 K K T Y G G Y Q G 2 109 Q G R V F L K G
G 2 111 R V F L K G G S D 2 112 V F L K G G S D S 2 113 F L K G G S
D S D 2 120 S D A S L V I T D 2 126 I T D L T L E D Y 2 131 L E D Y
G R Y K C 2 136 R Y K C E V I E G 2 147 D D T V V V A L D 2 165 P R
L G R Y N L N 2 182 L D Q D A V I A S 2 184 Q D A V I A S F D 2 190
S F D Q L Y D A W 2 195 Y D A W R G G L D 2 201 G L D W C N A G W 2
208 G W L S D G S V Q 2 222 P R E P C G G Q N 2 230 N T V P G V R N
Y 2 240 F W D K D K S R Y 2 247 R Y D V F C F T S 2 248 Y D V F C F
T S N 2 254 T S N F N G R F Y 2 265 I H P T K L T Y D 2 282 D G A Q
I A K V G 2 283 G A Q I A K V G Q 2 300 G Y D R C D A G W 2 314 V R
Y P I S R P R 2 325 C S P T E A A V R 2 332 V R F V G F P D K 2 345
Y G V Y C F R A Y 2 346 G V Y C F R A Y N 2 8 V L I S I C W A D 1
13 C W A D H L S D N 1 14 W A D H L S D N Y 1 25 D H D R A I H I Q
1 30 I H I Q A E N G P 1 38 P H L L V E A E Q 1 40 L L V E A E Q A
K 1 54 G G N V T L P C K 1 57 V T L P C K F Y R 1 58 T L P C K F Y
R D 1 67 P T A F G S G I H 1 94 V F V S M G Y H K 1 97 S M G Y H K
K T Y 1 98 M G Y H K K T Y G 1 100 Y H K K T Y G G Y 1 101 H K K T
Y G G Y Q 1 124 L V I T D L T L E 1 130 T L E D Y G R Y K 1 138 K C
E V I E G L E 1 140 E V I E G L E D D 1 157 Q G V V F P Y F P 1 162
P Y F P R L G R Y 1 163 Y F P R L G R Y N 1 170 Y N L N F H E A Q 1
171 N L N F H E A Q Q 1 173 N F H E A Q Q A C 1 175 H E A Q Q A C L
D 1 187 V I A S F D Q L Y 1 191 F D Q L Y D A W R 1 200 G G L D W C
N A G 1 203 D W C N A G W L S 1 206 N A G W L S D G S 1 216 Q Y P I
T K P R E 1 228 G Q N T V P G V R 1 233 P G V R N Y G F W 1 235 V R
N Y G F W D K 1 237 N Y G F W D K D K 1 250 V F C F T S N F N 1 252
C F T S N F N G R 1 255 S N F N G R F Y Y 1 261 F Y Y L I H P T K 1
273 D E A V Q A C L N 1 277 Q A C L N D G A Q 1 289 V G Q I F A A W
K 1 299 L G Y D R C D A G 1 305 D A G W L A D G S 1 319 S R P R R R
C S P 1 335 V G F P D K K H K 1 151P3D4 v.2: HLA Peptide Scoring
Results B*0702 9-mers SYFPEITHI 308 S P Y G P R N P L 27 228 S P R
G L G F I F 21 240 A P L A A T R A T 21 252 H P G G R T P R A 21
274 A P V P A A S P A 20 266 R P P A L S A R A 19 39 V P T K V T G
I I 18 125 N P S R R P Y H F 18 152 C P Q G H A S E A 18 371 A G S
G Y C G A L 17 9 F P L R A L H I V 16 81 K Q R K D K V L L 16 264 A
H R P P A L S A 16 279 A S P A A W L P L 16 311 G P R N P L P N P
16 271 S A R A P V P A A 15 277 P A A S P A A W L 15 322 S P S G G
G G L K 15 6 T K T F P L R A L 14 30 K Q D K K V D L L 14 129 R P Y
H F Q V P S 14 176 K Y Q A V T A T L 14 223 S P G G G S P R G 14
257 T P R A G S S A H 14 276 V P A A S P A A W 14 293 R P S S C P T
S S 14 399 R K A E N G P H L 14 3 E H T T K T F P L 13 104 S G S F
C R N K L 13 110 N K L K Y L A F L 13 135 V P S R I F W R Q 13 158
S E A Y K K V C L 13 169 A P H E V G W K Y 13 224 P G G G S P R G L
13 234 F I F K T I A P L 13 237 K T I A P L A A T 13 262 S S A H R
P P A L 13 280 S P A A W L P L R 13 362 V E N G R P A D L 13 378 A
L W K A I E S L 13 29 M K Q D K K V D L 12 80 E K Q R K D K V L 12
107 F C R N K L K Y L 12 197 R K N K Q L M R L 12 226 G G S P R G L
G F 12 249 R I G H P G G R T 12 261 G S S A H R P P A 12 267 P P A
L S A R A P 12 299 T S S S T Y D S L 12 316 L P N P R H S P S 12
318 N P R H S P S G G 12 331 K P A R H C Q G Q 12 336 C Q G Q K H N
V L 12 366 R P A D L A G S G 12 382 A I E S L E E G L 12 36 D L L V
P T K V T 11 51 A K D F G H V Q F 11 52 K D F G H V Q F V 11 186 E
K R K E K A E I 11 194 I H Y R K N K Q L 11 297 C P T S S S T Y D
11 314 N P L P N P R H S 11 321 H S P S G G G G L 11 348 K P Q R K
P K S E 11 352 K P K S E N N S W 11 363 E N G R P A D L A 11 400 K
A E N G P H L L 11 10 P L R A L H I V V 10 33 K K V D L L V P T 10
57 V Q F V G S Y K L 10 87 V L L G R K A V V 10 88 L L G R K A V V
V 10 109 R N K L K Y L A F 10 165 C L S G A P H E V 10 270 L S A R
A P V P A 10 285 L P L R T P W T R 10 289 T P W T R P S S C 10 291
W T R P S S C P T 10 325 G G G G L K K P A 10 13 A L H I V V E S I
9 21 I R D H S G Q K M 9 31 Q D K K V D L L V 9 49 Q G A K D F G H
V 9 68 S N D G E H W T V 9 86 K V L L G R K A V 9 95 V V S C E G I
N I 9 116 A F L H K R M N T 9 127 S R R P Y H F Q V 9 132 H F Q V P
S R I F 9 149 G S C C P Q G H A 9 172 E V G W K Y Q A V 9 173 V G W
K Y Q A V T 9 175 W K Y Q A V T A T 9 195 H Y R K N K Q L M 9 230 R
G L G F I F K T 9 236 F K T I A P L A A 9 268 P A L S A R A P V 9
275 P V P A A S P A A 9 281 P A A W L P L R T 9 337 Q G Q K H N V L
A 9 375 Y C G A L W K A I 9 5 T T K T F P L R A 8 8 T F P L R A L H
I 8 27 Q K M K Q D K K V 8 38 L V P T K V T G I 8 43 V T G I I T Q
G A 8 58 Q F V G S Y K L A 8 93 A V V V S C E G I 8 156 H A S E A Y
K K V 8 171 H E V G W K Y Q A 8 174 G W K Y Q A V T A 8 209 A E K N
M K K K I 8 231 G L G F I F K T I 8 235 I F K T I A P L A 8 239 I A
P L A A T R A 8 242 L A A T R A T R I 8 256 R T P R A G S S A 8 284
W L P L R T P W T 8 335 H C Q G Q K H N V 8 360 W Y V E N G R P A 8
374 G Y C G A L W K A 8 1 M L E H T T K T F 7 35 V D L L V P T K V
7 40 P T K V T G I I T 7 46 I I T Q G A K D F 7 85 D K V L L G R K
A 7 89 L G R K A V V V S 7 99 E G I N I S G S F 7 108 C R N K L K Y
L A 7 114 Y L A F L H K R M 7 138 R I F W R Q E K A 7 184 L E E K R
K E K A 7 201 Q L M R L Q K Q A 7 213 M K K K I D K Y T 7 227 G S P
R G L G F I 7 232 L G F I F K T I A 7 254 G G R T P R A G S 7 269 A
L S A R A P V P 7 295 S S C P T S S S T 7 345 A R G K P Q R K P 7
354 K S E N N S W Y V 7 370 L A G S G Y C G A 7 393 K Q K D K E R K
A 7 67 Y S N D G E H W T 6 79 D E K Q R K D K V 6 126 P S R R P Y H
F Q 6 131 Y H F Q V P S R I 6 146 A D G G S C C P Q 6 161 Y K K V C
L S G A 6 166 L S G A P H E V G 6 205 L Q K Q A E K N M 6 244 A T R
A T R I G H 6 272 A R A P V P A A S 6 283 A W L P L R T P W 6 286 P
L R T P W T R P 6 294 P S S C P T S S S 6 323 P S G G G G L K K 6
349 P Q R K P K S E N 6 364 N G R P A D L A G 6 66 A Y S N D G E H
W 5 83 R K D K V L L G R 5 102 N I S G S F C R N 5 160 A Y K K V C
L S G 5 222 E S P G G G S P R 5 225 G G G S P R G L G 5 247 A T R I
G H P G G 5 251 G H P G G R T P R 5 260 A G S S A H R P P 5 273 R A
P V P A A S P 5 278 A A S P A A W L P 5 282 A A W L P L R T P 5 306
S L S P Y G P R N 5 313 R N P L P N P R H 5 320 R H S P S G G G G 5
7 K T F P L R A L H 4 11 L R A L H I V V E 4 12 R A L H I V V E S 4
23 D H S G Q K M K Q 4 34 K V D L L V P T K 4 42 K V T G I I T Q G
4 47 I T Q G A K D F G 4 59 F V G S Y K L A Y 4 90 G R K A V V V S
C 4 119 H K R M N T N P S 4 145 K A D G G S C C P 4 157 A S E A Y K
K V C 4 163 K V C L S G A P H 4 167 S G A P H E V G W 4 216 K I D K
Y T E S P 4 220 Y T E S P G G G S 4 221 T E S P G G G S P 4 241 P L
A A T R A T R 4 258 P R A G S S A H R 4 263 S A H R P P A L S 4 305
D S L S P Y G P R 4 315 P L P N P R H S P 4 328 G L K K P A R H C 4
338 G Q K H N V L A R 4 344 L A R G K P Q R K 4 346 R G K P Q R K P
K 4 369 D L A G S G Y C G 4 384 E S L E E G L G G 4 394 Q K D K E R
K A E 4 397 K E R K A E N G P 4 4 H T T K T F P L R 3 32 D K K V D
L L V P 3 37 L L V P T K V T G 3 54 F G H V Q F V G S 3 60 V G S Y
K L A Y S 3 69 N D G E H W T V Y 3 70 D G E H W T V Y Q 3 82 Q R K
D K V L L G 3 91 R K A V V V S C E 3 112 L K Y L A F L H K 3 120 K
R M N T N P S R 3 122 M N T N P S R R P 3 123 N T N P S R R P Y 3
128 R R P Y H F Q V P 3 133 F Q V P S R I F W 3 140 F W R Q E K A D
G 3 144 E K A D G G S C C 3 150 S C C P Q G H A S 3 159 E A Y K K V
C L S 3 178 Q A V T A T L E E 3 179 A V T A T L E E K 3 192 A E I H
Y R K N K 3 199 N K Q L M R L Q K 3 202 L M R L Q K Q A E 3 211 K N
M K K K I D K 3 229 P R G L G F I F K 3 238 T I A P L A A T R 3 243
A A T R A T R I G 3 246 R A T R I G H P G 3 250 I G H P G G R T P 3
287 L R T P W T R P S 3 288 R T P W T R P S S 3 290 P W T R P S S C
P 3 298 P T S S S T Y D S 3 309 P Y G P R N P L P 3 310 Y G P R N P
L P N 3 319 P R H S P S G G G 3 324 S G G G G L K K P 3 326 G G G L
K K P A R 3 333 A R H C Q G Q K H 3 342 N V L A R G K P Q 3 356 E N
N S W Y V E N 3 357 N N S W Y V E N G 3 361 Y V E N G R P A D 3 368
A D L A G S G Y C 3 372 G S G Y C G A L W 3 380 W K A I E S L E E 3
383 I E S L E E G L G 3 386 L E E G L G G K Q 3 387 E E G L G G K Q
K 3 388 E G L G G K Q K D 3 389 G L G G K Q K D K 3 398 E R K A E N
G P H 3 2 L E H T T K T F P 2 18 V E S I R D H S G 2 20 S I R D H S
G Q K 2 28 K M K Q D K K V D 2 45 G I I T Q G A K D 2 48 T Q G A K
D F G H 2 50 G A K D F G H V Q 2 53 D F G H V Q F V G 2 64 K L A Y
S N D G E 2 78 Q D E K Q R K D K 2 97 S C E G I N I S G 2 100 G I N
I S G S F C 2 103 I S G S F C R N K 2 106 S F C R N K L K Y 2 113 K
Y L A F L H K R 2 124 T N P S R R P
Y H 2 130 P Y H F Q V P S R 2 136 P S R I F W R Q E 2 139 I F W R Q
E K A D 2 142 R Q E K A D G G S 2 143 Q E K A D G G S C 2 147 D G G
S C C P Q G 2 148 G G S C C P Q G H 2 153 P Q G H A S E A Y 2 154 Q
G H A S E A Y K 2 162 K K V C L S G A P 2 177 Y Q A V T A T L E 2
182 A T L E E K R K E 2 185 E E K R K E K A E 2 188 R K E K A E I H
Y 2 189 K E K A E I H Y R 2 190 E K A E I H Y R K 2 196 Y R K N K Q
L M R 2 204 R L Q K Q A E K N 2 207 K Q A E K N M K K 2 215 K K I D
K Y T E S 2 217 I D K Y T E S P G 2 233 G F I F K T I A P 2 248 T R
I G H P G G R 2 253 P G G R T P R A G 2 259 R A G S S A H R P 2 265
H R P P A L S A R 2 300 S S S T Y D S L S 2 301 S S T Y D S L S P 2
303 T Y D S L S P Y G 2 304 Y D S L S P Y G P 2 312 P R N P L P N P
R 2 327 G G L K K P A R H 2 329 L K K P A R H C Q 2 330 K K P A R H
C Q G 2 332 P A R H C Q G Q K 2 343 V L A R G K P Q R 2 351 R K P K
S E N N S 2 353 P K S E N N S W Y 2 365 G R P A D L A G S 2 367 P A
D L A G S G Y 2 373 S G Y C G A L W K 2 376 C G A L W K A I E 2 390
L G G K Q K D K E 2 395 K D K E R K A E N 2 16 I V V E S I R D H 1
17 V V E S I R D H S 1 19 E S I R D H S G Q 1 22 R D H S G Q K M K
1 24 H S G Q K M K Q D 1 25 S G Q K M K Q D K 1 44 T G I I T Q G A
K 1 55 G H V Q F V G S Y 1 56 H V Q F V G S Y K 1 61 G S Y K L A Y
S N 1 63 Y K L A Y S N D G 1 71 G E H W T V Y Q D 1 72 E H W T V Y
Q D E 1 77 Y Q D E K Q R K D 1 84 K D K V L L G R K 1 92 K A V V V
S C E G 1 98 C E G I N I S G S 1 101 I N I S G S F C R 1 111 K L K
Y L A F L H 1 117 F L H K R M N T N 1 118 L H K R M N T N P 1 121 R
M N T N P S R R 1 137 S R I F W R Q E K 1 151 C C P Q G H A S E 1
155 G H A S E A Y K K 1 164 V C L S G A P H E 1 168 G A P H E V G W
K 1 180 V T A T L E E K R 1 183 T L E E K R K E K 1 187 K R K E K A
E I H 1 191 K A E I H Y R K N 1 193 E I H Y R K N K Q 1 198 K N K Q
L M R L Q 1 200 K Q L M R L Q K Q 1 203 M R L Q K Q A E K 1 206 Q K
Q A E K N M K 1 208 Q A E K N M K K K 1 210 E K N M K K K I D 1 212
N M K K K I D K Y 1 214 K K K I D K Y T E 1 218 D K Y T E S P G G 1
219 K Y T E S P G G G 1 245 T R A T R I G H P 1 255 G R T P R A G S
S 1 292 T R P S S C P T S 1 302 S T Y D S L S P Y 1 317 P N P R H S
P S G 1 334 R H C Q G Q K H N 1 339 Q K H N V L A R G 1 340 K H N V
L A R G K 1 341 H N V L A R G K P 1 347 G K P Q R K P K S 1 350 Q R
K P K S E N N 1 355 S E N N S W Y V E 1 379 L W K A I E S L E 1 381
K A I E S L E E G 1 392 G K Q K D K E R K 1
[0829]
36TABLE XXIX SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:
HLA Peptide Scoring Results B*08 9-mers SYFPEITHI 76 K I R I K W T
K L 30 164 F P R L G R Y N L 24 243 K D K S R Y D V F 24 134 Y G R
Y K C E V I 23 232 V P G V R N Y G F 23 329 E A A V R F V G F 22 74
I H K I R I K W T 21 81 W T K L T S D Y L 21 336 G F P D K K H K L
21 51 S H R G G N V T L 20 241 W D K D K S R Y D 20 320 R P R R R C
S P T 20 339 D K K H K L Y G V 20 88 Y L K E V D V F V 19 219 I T K
P R E P C G 19 123 S L V I T D L T L 18 256 N F N G R F Y Y L 18
337 F P D K K H K L Y 18 113 F L K G G S D S D 17 217 Y P I T K P R
E P 17 284 A Q I A K V G Q I 17 326 S P T E A A V R F 17 58 T L P C
K F Y R D 16 121 D A S L V I T D L 16 286 I A K V G Q I F A 16 293
F A A W K I L G Y 16 301 Y D R C D A G W L 16 46 Q A K V F S H R G
15 146 E D D T V V V A L 15 291 Q I F A A W K I L 15 318 I S R P R
R R C S 15 24 L D H D R A I H I 14 33 Q A E N G P H L L 14 78 R I K
W T K L T S 14 86 S D Y L K E V D V 14 153 A L D L Q G V V F 14 221
K P R E P C G G Q 14 245 K S R Y D V F C F 14 316 Y P I S R P R R R
14 4 L L L L V L I S I 13 32 I Q A E N G P H L 13 72 S G I H K I R
I K 13 137 Y K C E V I E G L 13 166 R L G R Y N L N F 13 66 D P T A
F G S G I 12 106 G G Y Q G R V F L 12 136 R Y K C E V I E G 12 239
G F W D K D K S R 12 267 P T K L T Y D E A 12 341 K H K L Y G V Y C
12 1 M K S L L L L V L 11 10 I S I C W A D H L 11 16 D H L S D N Y
T L 11 44 A E Q A K V F S H 11 79 I K W T K L T S D 11 99 G Y H K K
T Y G G 11 101 H K K T Y G G Y Q 11 111 R V F L K G G S D 11 116 G
G S D S D A S L 11 132 E D Y G R Y K C E 11 148 D T V V V A L D L
11 159 V V F P Y F P R L 11 174 F H E A Q Q A C L 11 265 I H P T K
L T Y D 11 3 S L L L L V L I S 10 37 G P H L L V E A E 10 42 V E A
E Q A K V F 10 60 P C K F Y R D P T 10 98 M G Y H K K T Y G 10 100
Y H K K T Y G G Y 10 107 G Y Q G R V F L K 10 186 A V I A S F D Q L
10 194 L Y D A W R G G L 10 202 L D W C N A G W L 10 262 Y Y L I H
P T K L 10 272 Y D E A V Q A C L 10 285 Q I A K V G Q I F 10 295 A
W K I L G Y D R 10 313 S V R Y P I S R P 10 319 S R P R R R C S P
10 338 P D K K H K L Y G 10 40 L L V E A E Q A K 9 49 V F S H R G G
N V 9 61 C K F Y R D P T A 9 299 L G Y D R C D A G 9 311 D G S V R
Y P I S 9 342 H K L Y G V Y C F 9 2 K S L L L L V L I 8 5 L L L V L
I S I C 8 8 V L I S I C W A D 8 39 H L L V E A E Q A 8 109 Q G R V
F L K G G 8 118 S D S D A S L V I 8 144 G L E D D T V V V 8 162 P Y
F P R L G R Y 8 165 P R L G R Y N L N 8 195 Y D A W R G G L D 8 201
G L D W C N A G W 8 211 S D G S V Q Y P I 8 224 E P C G G Q N T V 8
253 F T S N F N G R F 8 298 I L G Y D R C D A 8 6 L L V L I S I C W
7 17 H L S D N Y T L D 7 22 Y T L D H D R A I 7 26 H D R A I H I Q
A 7 43 E A E Q A K V F S 7 55 G N V T L P C K F 7 62 K F Y R D P T
A F 7 63 F Y R D P T A F G 7 69 A F G S G I H K I 7 71 G S G I H K
I R I 7 87 D Y L K E V D V F 7 105 Y G G Y Q G R V F 7 128 D L T L
E D Y G R 7 155 D L Q G V V F P Y 7 156 L Q G V V F P Y F 7 161 F P
Y F P R L G R 7 167 L G R Y N L N F H 7 181 C L D Q D A V I A 7 183
D Q D A V I A S F 7 209 W L S D G S V Q Y 7 234 G V R N Y G F W D 7
257 F N G R F Y Y L I 7 263 Y L I H P T K L T 7 266 H P T K L T Y D
E 7 269 K L T Y D E A V Q 7 290 G Q I F A A W K I 7 308 W L A D G S
V R Y 7 322 R R R C S P T E A 7 11 S I C W A D H L S 6 23 T L D H D
R A I H 6 31 H I Q A E N G P H 6 59 L P C K F Y R D P 6 83 K L T S
D Y L K E 6 125 V I T D L T L E D 6 130 T L E D Y G R Y K 6 171 N L
N F H E A Q Q 6 176 E A Q Q A C L D Q 6 179 Q A C L D Q D A V 6 180
A C L D Q D A V I 6 193 Q L Y D A W R G G 6 197 A W R G G L D W C 6
249 D V F C F T S N F 6 258 N G R F Y Y L I H 6 274 E A V Q A C L N
D 6 277 Q A C L N D G A Q 6 278 A C L N D G A Q I 6 279 C L N D G A
Q I A 6 283 G A Q I A K V G Q 6 310 A D G S V R Y P I 6 321 P R R R
C S P T E 6 331 A V R F V G F P D 6 343 K L Y G V Y C F R 6 28 R A
I H I Q A E N 5 73 G I H K I R I K W 5 141 V I E G L E D D T 5 152
V A L D L Q G V V 5 187 V I A S F D Q L Y 5 188 I A S F D Q L Y D 5
309 L A D G S V R Y P 5 330 A A V R F V G F P 5 9 L I S I C W A D H
4 14 W A D H L S D N Y 4 29 A I H I Q A E N G 4 68 T A F G S G I H
K 4 91 E V D V F V S M G 4 97 S M G Y H K K T Y 4 140 E V I E G L E
D D 4 143 E G L E D D T V V 4 185 D A V I A S F D Q 4 196 D A W R G
G L D W 4 206 N A G W L S D G S 4 214 S V Q Y P I T K P 4 218 P I T
K P R E P C 4 264 L I H P T K L T Y 4 271 T Y D E A V Q A C 4 294 A
A W K I L G Y D 4 297 K I L G Y D R C D 4 305 D A G W L A D G S 4
317 P I S R P R R R C 4 19 S D N Y T L D H D 3 120 S D A S L V I T
D 3 173 N F H E A Q Q A C 3 190 S F D Q L Y D A W 3 27 D R A I H I
Q A E 2 35 E N G P H L L V E 2 36 N G P H L L V E A 2 38 P H L L V
E A E Q 2 45 E Q A K V F S H R 2 52 H R G G N V T L P 2 54 G G N V
T L P C K 2 56 N V T L P C K F Y 2 70 F G S G I H K I R 2 77 I R I
K W T K L T 2 84 L T S D Y L K E V 2 89 L K E V D V F V S 2 96 V S
M G Y H K K T 2 126 I T D L T L E D Y 2 129 L T L E D Y G R Y 2 135
G R Y K C E V I E 2 142 I E G L E D D T V 2 145 L E D D T V V V A 2
147 D D T V V V A L D 2 151 V V A L D L Q G V 2 154 L D L Q G V V F
P 2 160 V F P Y F P R L G 2 168 G R Y N L N F H E 2 169 R Y N L N F
H E A 2 182 L D Q D A V I A S 2 191 F D Q L Y D A W R 2 200 G G L D
W C N A G 2 215 V Q Y P I T K P R 2 227 G G Q N T V P G V 2 229 Q N
T V P G V R N 2 235 V R N Y G F W D K 2 246 S R Y D V F C F T 2 251
F C F T S N F N G 2 255 S N F N G R F Y Y 2 259 G R F Y Y L I H P 2
260 R F Y Y L I H P T 2 261 F Y Y L I H P T K 2 276 V Q A C L N D G
A 2 287 A K V G Q I F A A 2 332 V R F V G F P D K 2 334 F V G F P D
K K H 2 335 V G F P D K K H K 2 345 Y G V Y C F R A Y 2 7 L V L I S
I C W A 1 12 I C W A D H L S D 1 15 A D H L S D N Y T 1 21 N Y T L
D H D R A 1 25 D H D R A I H I Q 1 30 I H I Q A E N G P 1 50 F S H
R G G N V T 1 57 V T L P C K F Y R 1 75 H K I R I K W T K 1 85 T S
D Y L K E V D 1 90 K E V D V F V S M 1 92 V D V F V S M G Y 1 93 D
V F V S M G Y H 1 94 V F V S M G Y H K 1 95 F V S M G Y H K K 1 102
K K T Y G G Y Q G 1 110 G R V F L K G G S 1 112 V F L K G G S D S 1
115 K G G S D S D A S 1 117 G S D S D A S L V 1 119 D S D A S L V I
T 1 122 A S L V I T D L T 1 131 L E D Y G R Y K C 1 133 D Y G R Y K
C E V 1 138 K C E V I E G L E 1 139 C E V I E G L E D 1 149 T V V V
A L D L Q 1 150 V V V A L D L Q G 1 157 Q G V V F P Y F P 1 158 G V
V F P Y F P R 1 170 Y N L N F H E A Q 1 175 H E A Q Q A C L D 1 184
Q D A V I A S F D 1 192 D Q L Y D A W R G 1 199 R G G L D W C N A 1
207 A G W L S D G S V 1 208 G W L S D G S V Q 1 210 L S D G S V Q Y
P 1 212 D G S V Q Y P I T 1 213 G S V Q Y P I T K 1 225 P C G G Q N
T V P 1 226 C G G Q N T V P G 1 228 G Q N T V P G V R 1 230 N T V P
G V R N Y 1 237 N Y G F W D K D K 1 240 F W D K D K S R Y 1 244 D K
S R Y D V F C 1 247 R Y D V F C F T S 1 250 V F C F T S N F N 1 268
T K L T Y D E A V 1 270 L T Y D E A V Q A 1 273 D E A V Q A C L N 1
280 L N D G A Q I A K 1 281 N D G A Q I A K V 1 282 D G A Q I A K V
G 1 288 K V G Q I F A A W 1 289 V G Q I F A A W K 1 292 I F A A W K
I L G 1 296 W K I L G Y D R C 1 300 G Y D R C D A G W 1 303 R C D A
G W L A D 1 306 A G W L A D G S V 1 307 G W L A D G S V R 1 312 G S
V R Y P I S R 1 314 V R Y P I S R P R 1 323 R R C S P T E A A 1 324
R C S P T E A A V 1 327 P T E A A V R F V 1 344 L Y G V Y C F R A 1
346 G V Y C F R A Y N 1 151P3D4 v.2: HLA Peptide Scoring Results
B*08 9-mers SYFPEITHI 107 F C R N K L K Y L 28 109 R N K L K Y L A
F 28 158 S E A Y K K V C L 24 185 E E K R K E K A E 24 80 E K Q R K
D K V L 23 194 I H Y R K N K Q L 23 391 G G K Q K D K E R 23 3 E H
T T K T F P L 22 187 K R K E K A E I H 22 26 G Q K M K Q D K K 21
29 M K Q D K K V D L 21 30 K Q D K K V D L L 21 82 Q R K D K V L L
G 21 212 N M K K K I D K Y 21 262 S S A H R P P A L 21 395 K D K E
R K A E N 21 125 N P S R R P Y H F 20 183 T L E E K R K E K 20 196
Y R K N K Q L M R 20 228 S P R G L G F I F 20 336 C Q G Q K H N V L
20 344 L A R G K P Q R K 20 350 Q R K P K S E N N 20 393 K Q K D K
E R K A 20 362 V E N G R P A D L 19 79 D E K Q R K D K V 18 242 L A
A T R A T R I 18 308 S P Y G P R N P L 18 389 G L G G K Q K D K 18
38 L V P T K V T G I 17 81 K Q R K D K V L L 17 88 L L G R K A V V
V 17 111 K L K Y L A F L H 17 159 E A Y K K V C L S 17 209 A E K N
M K K K I 17 328 G L K K P A R H C 17 348 K P Q R K P K S E 17 352
K P K S E N N S W 17 378 A L W K A I E S L 17 234 F I F K T I A P L
16 377 G A L W K A I E S 16 8 T F P L R A L H I 15 50 G A K D F G H
V Q 15 87 V L L G R K A V V 15 117 F L H K R M N T N 15 186 E K R K
E K A E I 15 193 E I H Y R K N K Q 15 226 G G S P R G L G F 15 252
H P G G R T P R A 15 284 W L P L R T P W T 15 231 G L G F I F K T I
14 269 A L S A R A P V P 14 271 S A R A P V P A A 14 277 P A A S P
A A W L 14 289 T P W T R P S S C 14 316 L P N P R H S P S 14 382 A
I E S L E E G L 14 400 K A E N G P H L L 14 1 M L E H T T K T F 13
13 A L H I V V E S I 13 39 V P T K V T G I I 13 62 S Y K L A Y S N
D 13 90 G R K A V V V S C 13 172 E V G W K Y Q A V 13 174 G W K Y Q
A V T A 13 207 K Q A E K N M K K 13 210 E K N M K K K I D 13 257 T
P R A G S S A H 13 311 G P R N P L P N P 13 326 G G G L K K P A R
13 338 G Q K H N V L A R 13 398 E R K A E N G P H 13 10 P L R A L H
I V V 12 20 S I R D H S G Q K 12 24 H S G Q K M K Q D 12 46 I I T Q
G A K D F 12 57 V Q F V G S Y K L 12 60 V G S Y K L A Y S 12 77 Y Q
D E K Q R K D 12 104 S G S F C R N K L 12 138 R I F W R Q E K A 12
141 W R Q E K A D G G 12 217 I D K Y T E S P G 12 233 G F I F K T I
A P 12 286 P L R T P W T R P 12 318 N P R H S P S G G 12 399 R K A
E N G P H L 12 6 T K T F P L R A L 11 28 K M K Q D K K V D 11 32 D
K K V D L L V P 11 40 P T K V T G I I T 11 84 K D K V L L G R K 11
105 G S F C R N K L K 11 118 L H K R M N T N P 11 161 Y K K V C L S
G A 11 189 K E K A E I H Y R 11 203 M R L Q K Q A E K 11 205 L Q K
Q A E K N M 11 213 M K K K I D K Y T 11 215 K K I D K Y T E S 11
235 I F K T I A P L A 11 321 H S P S G G G G L 11 327 G G L K K P A
R H 11 346 R G K P Q R K P K 11 371 A G S G Y C G A L 11 5 T T K T
F P L R A 10 31 Q D K K V D L L V 10 48 T Q G A K D F G H 10 110 N
K L K Y L A F L 10 116 A F L H K R M N T 10 143 Q E K A D G G S C
10 160 A Y K K V C L S G 10 176 K Y Q A V T A T L 10 197 R K N K Q
L M R L 10 198 K N K Q L M R L Q 10 211 K N M K K K I D K 10 214 K
K K I D K Y T E 10 224 P G G G S P R G L 10 279 A S P A A W L P L
10 299 T S S S T Y D S L 10 329 L K K P A R H C Q 10 332 P A R H C
Q G Q K 10 379 L W K A I E S L E 10 385 S L E E G L G G K 10 396 D
K E R K A E N G 10 18 V E S I R D H S G 9 134 Q V P S R I F W R 9
245 T R A T R I G H P 9 255 G R T P R A G S S 9 309 P Y G P R N P L
P 9 342 N V L A R G K P Q 9 347 G K P Q R K P K S 9 36 D L L V P T
K V T 8 64 K L A Y S N D G E 8 89 L G R K A V V V S 8 99 E G I N I
S G S F 8 124 T N P S R R P Y H 8 127 S R R P Y H F Q V 8 132 H F Q
V P S R I F 8 156 H A S E A Y K K V 8 169 A P H E V G W K Y 8 184 L
E E K R K E K A 8 200 K Q L M R L Q K Q 8 202 L M R L Q K Q A E 8
223 S P G G G S P R G 8 267 P P A L S A R A P 8 276 V P A A S P A A
W 8 280 S P A A W L P L R 8 306 S L S P Y G P R N 8 322 S P S G G G
G L K 8 330 K K P A R H C Q G 8 375 Y C G A L W K A I 8 9 F P L R A
L H I V 7 12 R A L H I V V E S 7 37 L L V P T K V T G 7 51 A K D F
G H V Q F 7 93 A V V V S C E G I 7 95 V V S C E G I N I 7 114 Y L A
F L H K R M 7 119 H K R M N T N P S 7 129 R P Y H F Q V P S 7 135 V
P S R I F W R Q 7 140 F W R Q E K A D G 7 152 C P Q G H A S E A 7
165 C L S G A P H E V 7 195 H Y R K N K Q L M 7 201 Q L M R L Q K Q
A 7 227 G S P R G L G F I 7 240 A P L A A T R A T 7 254 G G R T P R
A G S 7 343 V L A R G K P Q R 7 349 P Q R K P K S E N 7 364 N G R P
A D L A G 7 381 K A I E S L E E G 7 15 H I V V E S I R D 6 92 K A V
V V S C E G 6 126 P S R R P Y H F Q 6 131 Y H F Q V P S R I 6 136 P
S R I F W R Q E 6 168 G A P H E V G W K 6 181 T A T L E E K R K 6
204 R L Q K Q A E K N 6 239 I A P L A A T R A 6 241 P L A A T R A T
R 6 244 A T R A T R I G H 6 247 A T R I G H P G G 6 263 S A H R P P
A L S 6 264 A H R P P A L S A 6 266 R P P A L S A R A 6 274 A P V P
A A S P A 6 285 L P L R T P W T R 6 291 W T R P S S C P T 6 293 R P
S S C P T S S 6 297 C P T S S S T Y D 6 314 N P L P N P R H S 6 315
P L P N P R H S P 6 331 K P A R H C Q G Q 6 366 R P A D L A G S G 6
369 D L A G S G Y C G 6 397 K E R K A E N G P 6 45 G I I T Q G A K
D 5 65 L A Y S N D G E H 5 100 G I N I S G S F C 5 115 L A F L H K
R M N 5 178 Q A V T A T L E E 5 208 Q A E K N M K K K 5 273 R A P V
P A A S P 5 282 A A W L P L R T P 5 367 P A D L A G S G Y 5 16 I V
V E S I R D H 4 96 V S C E G I N I S 4 102 N I S G S F C R N 4 145
K A D G G S C C P 4 190 E K A E I H Y R K 4 191 K A E I H Y R K N 4
216 K I D K Y T E S P 4 238 T I A P L A A T R 4 243 A A T R A T R I
G 4 246 R A T R I G H P G 4 249 R I G H P G G R T 4 259 R A G S S A
H R P 4 268 P A L S A R A P V 4 278 A A S P A A W L P 4 281 P A A W
L P L R T 4 356 E N N S W Y V E N 4 359 S W Y V E N G R P 4 370 L A
G S G Y C G A 4 384 E S L E E G L G G 4 387 E E G L G G K Q K 4 11
L R A L H I V V E 3 54 F G H V Q F V G S 3 73 H W T V Y Q D E K 3
86 K V L L G R K A V 3 97 S C E G I N I S G 3 137 S R I F W R Q E K
3 139 I F W R Q E K A D 3 150 S C C P Q G H A S 3 167 S G A P H E V
G W 3 301 S S T Y D S L S P 3 324 S G G G G L K K P 3 353 P K S E N
N S W Y 3 19 E S I R D H S G Q 2 25 S G Q K M K Q D K 2 34 K V D L
L V P T K 2 35 V D L L V P T K V 2 55 G H V Q F V G S Y 2 59 F V G
S Y K L A Y 2 68 S N D G E H W T V 2 69 N D G E H W T V Y 2 71 G E
H W T V Y Q D 2 72 E H W T V Y Q D E 2 91 R K A V V V S C E 2 106 S
F C R N K L K Y 2 144 E K A D G G S C C 2 170 P H E V G W K Y Q 2
175 W K Y Q A V T A T 2 182 A T L E E K R K E 2 219 K Y T E S P G G
G 2 222 E S P G G G S P R 2 236 F K T I A P L A A 2 265 H R P P A L
S A R 2 295 S S C P T S S S T 2 296 S C P T S S S T Y 2 300 S S S T
Y D S L S 2 302 S T Y D S L S P Y 2 313 R N P L P N P R H 2 325 G G
G G L K K P A 2 337 Q G Q K H N V L A 2 341 H N V L A R G K P 2 355
S E N N S W Y V E 2 360 W Y V E N G R P A 2 363 E N G R P A D L A 2
372 G S G Y C G A L W 2 373 S G Y C G A L W K 2 383 I E S L E E G L
G 2 388 E G L G G K Q K D 2 394 Q K D K E R K A E 2 4 H T T K T F P
L R 1 14 L H I V V E S I R 1 17 V V E S I R D H S 1 21 I R D H S G
Q K M 1 22 R D H S G Q K M K 1 27 Q K M K Q D K K V 1 33 K K V D L
L V P T 1 41 T K V T G I I T Q 1 42 K V T G I I T Q G 1 43 V T G I
I T Q G A 1 44 T G I I T Q G A K 1 47 I T Q
G A K D F G 1 52 K D F G H V Q F V 1 56 H V Q F V G S Y K 1 58 Q F
V G S Y K L A 1 61 G S Y K L A Y S N 1 70 D G E H W T V Y Q 1 74 W
T V Y Q D E K Q 1 75 T V Y Q D E K Q R 1 76 V Y Q D E K Q R K 1 78
Q D E K Q R K D K 1 85 D K V L L G R K A 1 94 V V V S C E G I N 1
98 C E G I N I S G S 1 101 I N I S G S F C R 1 103 I S G S F C R N
K 1 112 L K Y L A F L H K 1 120 K R M N T N P S R 1 128 R R P Y H F
Q V P 1 130 P Y H F Q V P S R 1 133 F Q V P S R I F W 1 148 G G S C
C P Q G H 1 149 G S C C P Q G H A 1 153 P Q G H A S E A Y 1 155 G H
A S E A Y K K 1 157 A S E A Y K K V C 1 162 K K V C L S G A P 1 163
K V C L S G A P H 1 164 V C L S G A P H E 1 171 H E V G W K Y Q A 1
173 V G W K Y Q A V T 1 177 Y Q A V T A T L E 1 179 A V T A T L E E
K 1 180 V T A T L E E K R 1 192 A E I H Y R K N K 1 199 N K Q L M R
L Q K 1 225 G G G S P R G L G 1 229 P R G L G F I F K 1 230 R G L G
F I F K T 1 237 K T I A P L A A T 1 250 I G H P G G R T P 1 251 G H
P G G R T P R 1 253 P G G R T P R A G 1 261 G S S A H R P P A 1 270
L S A R A P V P A 1 272 A R A P V P A A S 1 275 P V P A A S P A A 1
304 Y D S L S P Y G P 1 307 L S P Y G P R N P 1 334 R H C Q G Q K H
N 1 335 H C Q G Q K H N V 1 340 K H N V L A R G K 1 357 N N S W Y V
E N G 1 358 N S W Y V E N G R 1 361 Y V E N G R P A D 1 365 G R P A
D L A G S 1 374 G Y C G A L W K A 1 376 C G A L W K A I E 1 380 W K
A I E S L E E 1 392 G K Q K D K E R K 1
[0830]
37TABLE XXX SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:
HLA Peptide Scoring Results B*1510 9-mers SYFPEITHI 51 S H R G G N
V T L 25 16 D H L S D N Y T L 21 174 F H E A Q Q A C L 21 32 I Q A
E N G P H L 16 106 G G Y Q G R V F L 16 146 E D D T V V V A L 15
159 V V F P Y F P R L 15 1 M K S L L L L V L 13 30 I H I Q A E N G
P 13 33 Q A E N G P H L L 13 74 I H K I R I K W T 13 116 G G S D S
D A S L 13 137 Y K C E V I E G L 13 336 G F P D K K H K L 13 10 I S
I C W A D H L 12 100 Y H K K T Y G G Y 12 121 D A S L V I T D L 12
164 F P R L G R Y N L 12 262 Y Y L I H P T K L 12 265 I H P T K L T
Y D 12 272 Y D E A V Q A C L 12 341 K H K L Y G V Y C 12 25 D H D R
A I H I Q 11 38 P H L L V E A E Q 11 105 Y G G Y Q G R V F 11 123 S
L V I T D L T L 11 148 D T V V V A L D L 11 194 L Y D A W R G G L
11 202 L D W C N A G W L 11 256 N F N G R F Y Y L 11 301 Y D R C D
A G W L 11 326 S P T E A A V R F 11 329 E A A V R F V G F 11 42 V E
A E Q A K V F 10 76 K I R I K W T K L 10 81 W T K L T S D Y L 10 87
D Y L K E V D V F 10 153 A L D L Q G V V F 10 186 A V I A S F D Q L
10 291 Q I F A A W K I L 10 90 K E V D V F V S M 9 253 F T S N F N
G R F 9 55 G N V T L P C K F 8 62 K F Y R D P T A F 8 156 L Q G V V
F P Y F 8 243 K D K S R Y D V F 8 285 Q I A K V G Q I F 8 342 H K L
Y G V Y C F 8 144 G L E D D T V V V 7 183 D Q D A V I A S F 7 232 V
P G V R N Y G F 7 245 K S R Y D V F C F 7 308 W L A D G S V R Y 7
317 P I S R P R R R C 7 318 I S R P R R R C S 7 43 E A E Q A K V F
S 6 145 L E D D T V V V A 6 166 R L G R Y N L N F 6 229 Q N T V P G
V R N 6 230 N T V P G V R N Y 6 249 D V F C F T S N F 6 316 Y P I S
R P R R R 6 22 Y T L D H D R A I 5 35 E N G P H L L V E 5 89 L K E
V D V F V S 5 130 T L E D Y G R Y K 5 154 L D L Q G V V F P 5 209 W
L S D G S V Q Y 5 217 Y P I T K P R E P 5 219 I T K P R E P C G 5
328 T E A A V R F V G 5 71 G S G I H K I R I 4 85 T S D Y L K E V D
4 88 Y L K E V D V F V 4 104 T Y G G Y Q G R V 4 118 S D S D A S L
V I 4 135 G R Y K C E V I E 4 143 E G L E D D T V V 4 162 P Y F P R
L G R Y 4 213 G S V Q Y P I T K 4 216 Q Y P I T K P R E 4 224 E P C
G G Q N T V 4 226 C G G Q N T V P G 4 228 G Q N T V P G V R 4 240 F
W D K D K S R Y 4 254 T S N F N G R F Y 4 264 L I H P T K L T Y 4
271 T Y D E A V Q A C 4 282 D G A Q I A K V G 4 283 G A Q I A K V G
Q 4 286 I A K V G Q I F A 4 292 I F A A W K I L G 4 309 L A D G S V
R Y P 4 313 S V R Y P I S R P 4 314 V R Y P I S R P R 4 315 R Y P I
S R P R R 4 324 R C S P T E A A V 4 327 P T E A A V R F V 4 345 Y G
V Y C F R A Y 4 17 H L S D N Y T L D 3 27 D R A I H I Q A E 3 36 N
G P H L L V E A 3 37 G P H L L V E A E 3 45 E Q A K V F S H R 3 46
Q A K V F S H R G 3 50 F S H R G G N V T 3 52 H R G G N V T L P 3
54 G G N V T L P C K 3 57 V T L P C K F Y R 3 58 T L P C K F Y R D
3 59 L P C K F Y R D P 3 64 Y R D P T A F G S 3 72 S G I H K I R I
K 3 73 G I H K I R I K W 3 77 I R I K W T K L T 3 84 L T S D Y L K
E V 3 91 E V D V F V S M G 3 107 G Y Q G R V F L K 3 120 S D A S L
V I T D 3 129 L T L E D Y G R Y 3 134 Y G R Y K C E V I 3 140 E V I
E G L E D D 3 142 I E G L E D D T V 3 152 V A L D L Q G V V 3 160 V
F P Y F P R L G 3 163 Y F P R L G R Y N 3 180 A C L D Q D A V I 3
181 C L D Q D A V I A 3 182 L D Q D A V I A S 3 188 I A S F D Q L Y
D 3 193 Q L Y D A W R G G 3 200 G G L D W C N A G 3 208 G W L S D G
S V Q 3 212 D G S V Q Y P I T 3 218 P I T K P R E P C 3 222 P R E P
C G G Q N 3 225 P C G G Q N T V P 3 227 G G Q N T V P G V 3 231 T V
P G V R N Y G 3 241 W D K D K S R Y D 3 244 D K S R Y D V F C 3 270
L T Y D E A V Q A 3 287 A K V G Q I F A A 3 296 W K I L G Y D R C 3
297 K I L G Y D R C D 3 298 I L G Y D R C D A 3 307 G W L A D G S V
R 3 311 D G S V R Y P I S 3 332 V R F V G F P D K 3 335 V G F P D K
K H K 3 340 K K H K L Y G V Y 3 344 L Y G V Y C F R A 3 2 K S L L L
L V L I 2 5 L L L V L I S I C 2 12 I C W A D H L S D 2 13 C W A D H
L S D N 2 21 N Y T L D H D R A 2 23 T L D H D R A I H 2 34 A E N G
P H L L V 2 40 L L V E A E Q A K 2 47 A K V F S H R G G 2 61 C K F
Y R D P T A 2 63 F Y R D P T A F G 2 67 P T A F G S G I H 2 68 T A
F G S G I H K 2 69 A F G S G I H K I 2 70 F G S G I H K I R 2 75 H
K I R I K W T K 2 78 R I K W T K L T S 2 79 I K W T K L T S D 2 86
S D Y L K E V D V 2 93 D V F V S M G Y H 2 95 F V S M G Y H K K 2
97 S M G Y H K K T Y 2 99 G Y H K K T Y G G 2 103 K T Y G G Y Q G R
2 110 G R V F L K G G S 2 112 V F L K G G S D S 2 113 F L K G G S D
S D 2 119 D S D A S L V I T 2 125 V I T D L T L E D 2 126 I T D L T
L E D Y 2 131 L E D Y G R Y K C 2 132 E D Y G R Y K C E 2 133 D Y G
R Y K C E V 2 136 R Y K C E V I E G 2 138 K C E V I E G L E 2 141 V
I E G L E D D T 2 147 D D T V V V A L D 2 149 T V V V A L D L Q 2
155 D L Q G V V F P Y 2 157 Q G V V F P Y F P 2 158 G V V F P Y F P
R 2 161 F P Y F P R L G R 2 169 R Y N L N F H E A 2 170 Y N L N F H
E A Q 2 173 N F H E A Q Q A C 2 175 H E A Q Q A C L D 2 176 E A Q Q
A C L D Q 2 184 Q D A V I A S F D 2 190 S F D Q L Y D A W 2 192 D Q
L Y D A W R G 2 195 Y D A W R G G L D 2 197 A W R G G L D W C 2 205
C N A G W L S D G 2 210 L S D G S V Q Y P 2 214 S V Q Y P I T K P 2
215 V Q Y P I T K P R 2 220 T K P R E P C G G 2 221 K P R E P C G G
Q 2 238 Y G F W D K D K S 2 239 G F W D K D K S R 2 242 D K D K S R
Y D V 2 247 R Y D V F C F T S 2 255 S N F N G R F Y Y 2 261 F Y Y L
I H P T K 2 263 Y L I H P T K L T 2 268 T K L T Y D E A V 2 269 K L
T Y D E A V Q 2 273 D E A V Q A C L N 2 274 E A V Q A C L N D 2 277
Q A C L N D G A Q 2 279 C L N D G A Q I A 2 280 L N D G A Q I A K 2
288 K V G Q I F A A W 2 293 F A A W K I L G Y 2 299 L G Y D R C D A
G 2 303 R C D A G W L A D 2 304 C D A G W L A D G 2 312 G S V R Y P
I S R 2 321 P R R R C S P T E 2 322 R R R C S P T E A 2 323 R R C S
P T E A A 2 325 C S P T E A A V R 2 333 R F V G F P D K K 2 338 P D
K K H K L Y G 2 346 G V Y C F R A Y N 2 3 S L L L L V L I S 1 7 L V
L I S I C W A 1 8 V L I S I C W A D 1 9 L I S I C W A D H 1 24 L D
H D R A I H I 1 28 R A I H I Q A E N 1 39 H L L V E A E Q A 1 41 L
V E A E Q A K V 1 44 A E Q A K V F S H 1 48 K V F S H R G G N 1 49
V F S H R G G N V 1 56 N V T L P C K F Y 1 60 P C K F Y R D P T 1
80 K W T K L T S D Y 1 82 T K L T S D Y L K 1 96 V S M G Y H K K T
1 98 M G Y H K K T Y G 1 102 K K T Y G G Y Q G 1 108 Y Q G R V F L
K G 1 109 Q G R V F L K G G 1 114 L K G G S D S D A 1 115 K G G S D
S D A S 1 117 G S D S D A S L V 1 122 A S L V I T D L T 1 127 T D L
T L E D Y G 1 139 C E V I E G L E D 1 151 V V A L D L Q G V 1 165 P
R L G R Y N L N 1 167 L G R Y N L N F H 1 168 G R Y N L N F H E 1
178 Q Q A C L D Q D A 1 179 Q A C L D Q D A V 1 187 V I A S F D Q L
Y 1 189 A S F D Q L Y D A 1 196 D A W R G G L D W 1 198 W R G G L D
W C N 1 201 G L D W C N A G W 1 204 W C N A G W L S D 1 223 R E P C
G G Q N T 1 233 P G V R N Y G F W 1 234 G V R N Y G F W D 1 235 V R
N Y G F W D K 1 236 R N Y G F W D K D 1 246 S R Y D V F C F T 1 248
Y D V F C F T S N 1 252 C F T S N F N G R 1 259 G R F Y Y L I H P 1
260 R F Y Y L I H P T 1 266 H P T K L T Y D E 1 267 P T K L T Y D E
A 1 276 V Q A C L N D G A 1 281 N D G A Q I A K V 1 284 A Q I A K V
G Q I 1 290 G Q I F A A W K I 1 294 A A W K I L G Y D 1 300 G Y D R
C D A G W 1 302 D R C D A G W L A 1 310 A D G S V R Y P I 1 319 S R
P R R R C S P 1 330 A A V R F V G F P 1 334 F V G F P D K K H 1 337
F P D K K H K L Y 1 343 K L Y G V Y C F R 1 151P3D4 v.2: HLA
Peptide Scoring Results B*1510 9-mers SYFPEITHI 194 I H Y R K N K Q
L 22 3 E H T T K T F P L 21 6 T K T F P L R A L 15 131 Y H F Q V P
S R I 15 29 M K Q D K K V D L 14 81 K Q R K D K V L L 14 158 S E A
Y K K V C L 14 224 P G G G S P R G L 14 251 G H P G G R T P R 14
262 S S A H R P P A L 14 399 R K A E N G P H L 14 23 D H S G Q K M
K Q 13 55 G H V Q F V G S Y 13 80 E K Q R K D K V L 13 170 P H E V
G W K Y Q 13 197 R K N K Q L M R L 13 264 A H R P P A L S A 13 308
S P Y G P R N P L 13 320 R H S P S G G G G 13 336 C Q G Q K H N V L
13 340 K H N V L A R G K 13 371 A G S G Y C G A L 13 400 K A E N G
P H L L 13 30 K Q D K K V D L L 12 57 V Q F V G S Y K L 12 104 S G
S F C R N K L 12 155 G H A S E A Y K K 12 234 F I F K T I A P L 12
277 P A A S P A A W L 12 299 T S S S T Y D S L 12 334 R H C Q G Q K
H N 12 362 V E N G R P A D L 12 378 A L W K A I E S L 12 14 L H I V
V E S I R 11 72 E H W T V Y Q D E 11 110 N K L K Y L A F L 11 176 K
Y Q A V T A T L 11 321 H S P S G G G G L 11 382 A I E S L E E G L
11 46 I I T Q G A K D F 10 107 F C R N K L K Y L 10 114 Y L A F L H
K R M 10 118 L H K R M N T N P 10 132 H F Q V P S R I F 10 226 G G
S P R G L G F 10 279 A S P A A W L P L 10 51 A K D F G H V Q F 9
195 H Y R K N K Q L M 9 1 M L E H T T K T F 8 21 I R D H S G Q K M
8 125 N P S R R P Y H F 8 250 I G H P G G R T P 8 99 E G I N I S G
S F 7 109 R N K L K Y L A F 7 205 L Q K Q A E K N M 7 228 S P R G L
G F I F 7 11 L R A L H I V V E 6 16 I V V E S I R D H 6 37 L L V P
T K V T G 6 89 L G R K A V V V S 6 306 S L S P Y G P R N 6 314 N P
L P N P R H S 6 361 Y V E N G R P A D 6 122 M N T N P S R R P 5 123
M T N P S R R P Y 5 167 S G A P H E V G W 5 183 T L E E K R K E K 5
190 E K A E I H Y R K 5 221 T E S P G G G S P 5 223 S P G G G S P R
G 5 238 T I A P L A A T R 5 272 A R A P V P A A S 5 327 G G L K K P
A R H 5 328 G L K K P A R H C 5 392 G K Q K D K E R K 5 5 T T K T F
P L R A 4 12 R A L H I V V E S 4 28 K M K Q D K K V D 4 36 D L L V
P T K V T 4 41 T K V T G I I T Q 4 47 I T Q G A K D F G 4 50 G A K
D F G H V Q 4 76 V Y Q D E K Q R K 4 77 Y Q D E K Q R K D 4 87 V L
L G R K A V V 4 . 88 L L G R K A V V V 4 90 G R K A V V V S C 4 102
N I S G S F C R N 4 103 I S G S F C R N K 4 121 R M N T N P S R R 4
144 E K A D G G S C C 4 157 A S E A Y K K V C 4 165 C L S G A P H E
V 4 174 G W K Y Q A V T A 4 182 A T L E E K R K E 4 186 E K R K E K
A E I 4 198 K N K Q L M R L Q 4 208 Q A E K N M K K K 4 239 I A P L
A A T R A 4 252 H P G G R T P R A 4 253 P G G R T P R A G 4 261 G S
S A H R P P A 4 267 P P A L S A R A P 4 269 A L S A R A P V P 4 270
L S A R A P V P A 4 271 S A R A P V P A A 4 281 P A A W L P L R T 4
282 A A W L P L R T P 4 287 L R T P W T R P S 4 307 L S P Y G P R N
P 4 313 R N P L P N P R H 4 326 G G G L K K P A R 4 338 G Q K H N V
L A R 4 343 V L A R G K P Q R 4 344 L A R G K P Q R K 4 345 A R G K
P Q R K P 4 347 G K P Q R K P K S 4 349 P Q R K P K S E N 4 356 E N
N S W Y V E N 4 360 W Y V E N G R P A 4 388 E G L G G K Q K D 4 7 K
T F P L R A L H 3 15 H I V V E S I R D 3 32 D K K V D L L V P 3 33
K K V D L L V P T 3 34 K V D L L V P T K 3 54 F G H V Q F V G S 3
67 Y S N D G E H W T 3 69 N D G E H W T V Y 3 70 D G E H W T V Y Q
3 78 Q D E K Q R K D K 3 84 K D K V L L G R K 3 86 K V L L G R K A
V 3 91 R K A V V V S C E 3 96 V S C E G I N I S 3 101 I N I S G S F
C R 3 115 L A F L H K R M N 3 117 F L H K R M N T N 3 124 T N P S R
R P Y H 3 133 F Q V P S R I F W 3 135 V P S R I F W R Q 3 139 I F W
R Q E K A D 3 148 G G S C C P Q G H 3 150 S C C P Q G H A S 3 159 E
A Y K K V C L S 3 166 L S G A P H E V G 3 173 V G W K Y Q A V T 3
175 W K Y Q A V T A T 3 177 Y Q A V T A T L E 3 181 T A T L E E K R
K 3 184 L E E K R K E K A 3 191 K A E I H Y R K N 3 220 Y T E S P G
G G S 3 222 E S P G G G S P R 3 225 G G G S P R G L G 3 235 I F K T
I A P L A 3 240 A P L A A T R A T 3 241 P L A A T R A T R 3 242 L A
A T R A T R I 3 245 T R A T R I G H P 3 248 T R I G H P G G R 3 249
R I G H P G G R T 3 254 G G R T P R A G S 3 255 G R T P R A G S S 3
257 T P R A G S S A H 3 260 A G S S A H R P P 3 265 H R P P A L S A
R 3 276 V P A A S P A A W 3 278 A A S P A A W L P 3 283 A W L P L R
T P W 3 286 P L R T P W T R P 3 292 T R P S S C P T S 3 304 Y D S L
S P Y G P 3 309 P Y G P R N P L P 3 310 Y G P R N P L P N 3 311 G P
R N P L P N P 3 312 P R N P L P N P R 3 322 S P S G G G G L K 3 325
G G G G L K K P A 3 329 L K K P A R H C Q 3 337 Q G Q K H N V L A 3
346 R G K P Q R K P K 3 353 P K S E N N S W Y 3 359 S W Y V E N G R
P 3 364 N G R P A D L A G 3 383 I E S L E E G L G 3 385 S L E E G L
G G K 3 391 G G K Q K D K E R 3 393 K Q K D K E R K A 3 394 Q K D K
E R K A E 3 395 K D K E R K A E N 3 4 H T T K T F P L R 2 10 P L R
A L H I V V 2 17 V V E S I R D H S 2 24 H S G Q K M K Q D 2 25 S G
Q K M K Q D K 2 42 K V T G I I T Q G 2 44 T G I I T Q G A K 2 49 Q
G A K D F G H V 2 52 K D F G H V Q F V 2 53 D F G H V Q F V G 2 59
F V G S Y K L A Y 2 61 G S Y K L A Y S N 2 65 L A Y S N D G E H 2
68 S N D G E H W T V 2 71 G E H W T V Y Q D 2 73 H W T V Y Q D E K
2 75 T V Y Q D E K Q R 2 79 D E K Q R K D K V 2 82 Q R K D K V L L
G 2 85 D K V L L G R K A 2 92 K A V V V S C E G 2 97 S C E G I N I
S G 2 98 C E G I N I S G S 2 106 S F C R N K L K Y 2 108 C R N K L
K Y L A 2 127 S R R P Y H F Q V 2 128 R R P Y H F Q V P 2 129 R P Y
H F Q V P S 2 130 P Y H F Q V P S R 2 136 P S R I F W R Q E 2 137 S
R I F W R Q E K 2 140 F W R Q E K A D G 2 142 R Q E K A D G G S 2
145 K A D G G S C C P 2 149 G S C C P Q G H A 2 151 C C P Q G H A S
E 2 152 C P Q G H A S E A 2 156 H A S E A Y K K V 2 161 Y K K V C L
S G A 2 164 V C L S G A P H E 2 168 G A P H E V G W K 2 171 H E V G
W K Y Q A 2 172 E V G W K Y Q A V 2 185 E E K R K E K A E 2 188 R K
E K A E I H Y 2 193 E I H Y R K N K Q 2 202 L M R L Q K Q A E 2 203
M R L Q K Q A E K 2 207 K Q A E K N M K K 2 210 E K N M K K K I D 2
211 K N M K K K I D K 2 212 N M K K K I D K Y 2 214 K K K I D K Y T
E 2 215 K K I D K Y T E S 2 217 I D K Y T E S P G 2 219 K Y T E S P
G G G 2 227 G S P R G L G F I 2 230 R G L G F I F K T 2 231 G L G F
I F K T I 2 233 G F I F K T I A P 2 236 F K T I A P L A A 2 237 K T
I A P L A A T 2 243 A A T R A T R I G 2 247 A T R I G H P G G 2 258
P R A G S S A H R 2 259 R A G S S A H R P 2 263 S A H R P P A L S 2
266 R P P A L S A R A 2 273 R A P V P A A S P 2 274 A P V P A A S P
A 2 275 P V P A A S P A A 2 280 S P A A W L P L R 2 285 L P L R T P
W T R 2 288 R T P W T R P S S 2 289 T P W T R P S S C 2 291 W T R P
S S C P T 2 293 R P S S C P T S S 2 294 P S S C P T S S S 2 295 S S
C P T S S S T 2 303 T Y D S L S P Y G 2 315 P L P N P R H S P 2 316
L P N P R H S P S 2 323 P S G G G G L K K 2 324 S G G G G L K K P 2
335 H C Q G Q K H N V 2 339 Q K H N V L A R G 2 350 Q R K P K S E N
N 2 354 K S E N N S W Y V 2 355 S E N N S W Y V E 2 357 N N S W Y V
E N G 2 363 E N G R P A D L A 2 366 R P A D L A G S G 2 369 D L A G
S G Y C G 2 374 G Y C G A L W K A 2 375 Y C G A L W K A I 2 376 C G
A L W K A I E 2 377 G A L W K A I E S 2 380 W K A I E S L E E 2 381
K A I E S L E E
G 2 384 E S L E E G L G G 2 386 L E E G L G G K Q 2 387 E E G L G G
K Q K 2 389 G L G G K Q K D K 2 390 L G G K Q K D K E 2 2 L E H T T
K T F P 1 8 T F P L R A L H I 1 13 A L H I V V E S I 1 18 V E S I R
D H S G 1 19 E S I R D H S G Q 1 20 S I R D H S G Q K 1 22 R D H S
G Q K M K 1 26 G Q K M K Q D K K 1 27 Q K M K Q D K K V 1 31 Q D K
K V D L L V 1 35 V D L L V P T K V 1 38 L V F T K V T G I 1 39 V P
T K V T G I I 1 40 P T K V T G I I T 1 45 G I I T Q G A K D 1 48 T
Q G A K D F G H 1 58 Q F V G S Y K L A 1 60 V G S Y K L A Y S 1 63
Y K L A Y S N D G 1 64 K L A Y S N D G E 1 66 A Y S N D G E H W 1
83 R K D K V L L G R 1 93 A V V V S C E G I 1 95 V V S C E G I N I
1 100 G I N I S G S F C 1 105 G S F C R N K L K 1 116 A F L H K R M
N T 1 119 H K R M N T N P S 1 120 K R M N T N P S R 1 126 P S R R P
Y H F Q 1 134 Q V P S R I F W R 1 141 W R Q E K A D G G 1 146 A D G
G S C C P Q 1 147 D G G S C C P Q G 1 153 P Q G H A S E A Y 1 160 A
Y K K V C L S G 1 162 K K V C L S G A P 1 169 A P H E V G W K Y 1
178 Q A V T A T L E E 1 179 A V T A T L E E K 1 180 V T A T L E E K
R 1 187 K R K E K A E I H 1 189 K E K A E I H Y R 1 192 A E I H Y R
K N K 1 196 Y R K N K Q L M R 1 199 N K Q L M R L Q K 1 204 R L Q K
Q A E K N 1 206 Q K Q A E K N M K 1 209 A E K N M K K K I 1 213 M K
K K I D K Y T 1 216 K I D K Y T E S P 1 218 D K Y T E S P G G 1 229
P R G L G F I F K 1 232 L G F I F K T I A 1 244 A T R A T R I G H 1
268 P A L S A R A P V 1 284 W L P L R T P W T 1 290 P W T R P S S C
P 1 296 S C P T S S S T Y 1 298 P T S S S T Y D S 1 300 S S S T Y D
S L S 1 302 S T Y D S L S P Y 1 305 D S L S P Y G P R 1 317 P N P R
H S P S G 1 318 N P R H S P S G G 1 319 P R H S P S G G G 1 331 K P
A R H C Q G Q 1 341 H N V L A R G K P 1 348 K P Q R K P K S E 1 351
R K P K S E N N S 1 365 G R P A D L A G S 1 368 A D L A G S G Y C 1
370 L A G S G Y C G A 1 372 G S G Y C G A L W 1 373 S G Y C G A L W
K 1 396 D K E R K A E N G 1 397 K E R K A E N G P 1 398 E R K A E N
G P H 1
[0831]
38TABLE XXXI SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:
HLA Peptide Scoring Results B*2705 9-mers SYFPEITHI 332 V R F V G F
P D K 26 314 V R Y P I S R P R 25 235 V R N Y G F W D K 23 106 G G
Y Q G R V F L 20 333 R F V G F P D K K 19 103 K T Y G G Y Q G R 18
135 G R Y K C E V I E 18 166 R L G R Y N L N F 18 213 G S V Q Y P I
T K 18 259 G R F Y Y L I H P 18 315 R Y P I S R P R R 18 322 R R R
C S P T E A 18 51 S H R G G N V T L 17 55 G N V T L P C K F 17 68 T
A F G S G I H K 17 76 K I R I K W T K L 17 87 D Y L K E V D V F 17
116 G G S D S D A S L 17 121 D A S L V I T D L 17 159 V V F P Y F P
R L 17 168 G R Y N L N F H E 17 307 G W L A D G S V R 17 336 G F P
D K K H K L 17 343 K L Y G V Y C F R 17 62 K F Y R D P T A F 16 72
S G I H K I R I K 16 75 H K I R I K W T K 16 107 G Y Q G R V F L K
16 110 G R V F L K G G S 16 164 F P R L G R Y N L 16 183 D Q D A V
I A S F 16 239 G F W D K D K S R 16 249 D V F C F T S N F 16 261 F
Y Y L I H P T K 16 262 Y Y L I H P T K L 16 312 G S V R Y P I S R
16 342 H K L Y G V Y C F 16 1 M K S L L L L V L 15 16 D H L S D N Y
T L 15 52 H R G G N V T L P 15 54 G G N V T L P C K 15 77 I R I K W
T K L T 15 82 T K L T S D Y L K 15 137 Y K C E V I E G L 15 158 G V
V F P Y F P R 15 162 P Y F P R L G R Y 15 165 P R L G R Y N L N 15
186 A V I A S F D Q L 15 198 W R G G L D W C N 15 228 G Q N T V P G
V R 15 230 N T V P G V R N Y 15 280 L N D G A Q I A K 15 290 G Q I
F A A W K I 15 323 R R C S P T E A A 15 326 S P T E A A V R F 15
335 V G F P D K K H K 15 2 K S L L L L V L I 14 10 I S I C W A D H
L 14 20 D N Y T L D H D R 14 45 E Q A K V F S H R 14 57 V T L P C K
F Y R 14 69 A F G S G I H K I 14 80 K W T K L T S D Y 14 90 K E V D
V F V S M 14 95 F V S M G Y H K K 14 123 S L V I T D L T L 14 128 D
L T L E D Y G R 14 148 D T V V V A L D L 14 153 A L D L Q G V V F
14 161 F P Y F P R L G R 14 215 V Q Y P I T K P R 14 240 F W D K D
K S R Y 14 272 Y D E A V Q A C L 14 308 W L A D G S V R Y 14 316 Y
P I S R P R R R 14 325 C S P T E A A V R 14 340 K K H K L Y G V Y
14 4 L L L L V L I S I 13 27 D R A I H I Q A E 13 32 I Q A E N G P
H L 13 42 V E A E Q A K V F 13 70 F G S G I H K I R 13 71 G S G I H
K I R I 13 129 L T L E D Y G R Y 13 146 E D D T V V V A L 13 174 F
H E A Q Q A C L 13 191 F D Q L Y D A W R 13 209 W L S D G S V Q Y
13 243 K D K S R Y D V F 13 245 K S R Y D V F C F 13 246 S R Y D V
F C F T 13 253 F T S N F N G R F 13 255 S N F N G R F Y Y 13 256 N
F N G R F Y Y L 13 285 Q I A K V G Q I F 13 291 Q I F A A W K I L
13 293 F A A W K I L G Y 13 295 A W K I L G Y D R 13 321 P R R R C
S P T E 13 14 W A D H L S D N Y 12 33 Q A E N G P H L L 12 40 L L V
E A E Q A K 12 44 A E Q A K V F S H 12 64 Y R D P T A F G S 12 81 W
T K L T S D Y L 12 92 V D V F V S M G Y 12 93 D V F V S M G Y H 12
94 V F V S M G Y H K 12 155 D L Q G V V F P Y 12 156 L Q G V V F P
Y F 12 180 A C L D Q D A V I 12 222 P R E P C G G Q N 12 232 V P G
V R N Y G F 12 264 L I H P T K L T Y 12 284 A Q I A K V G Q I 12
289 V G Q I F A A W K 12 334 F V G F P D K K H 12 28 R A I H I Q A
E N 11 67 P T A F G S G I H 11 105 Y G G Y Q G R V F 11 126 I T D L
T L E D Y 11 202 L D W C N A G W L 11 237 N Y G F W D K D K 11 252
C F T S N F N G R 11 278 A C L N D G A Q I 11 301 Y D R C D A G W L
11 302 D R C D A G W L A 11 319 S R P R R R C S P 11 329 E A A V R
F V G F 11 337 F P D K K H K L Y 11 31 H I Q A E N G P H 10 56 N V
T L P C K F Y 10 97 S M G Y H K K T Y 10 100 Y H K K T Y G G Y 10
111 R V F L K G G S D 10 130 T L E D Y G R Y K 10 167 L G R Y N L N
F H 10 194 L Y D A W R G G L 10 211 S D G S V Q Y P I 10 236 R N Y
G F W D K D 10 260 R F Y Y L I H P T 10 9 L I S I C W A D H 9 18 L
S D N Y T L D H 9 22 Y T L D H D R A I 9 23 T L D H D R A I H 9 73
G I H K I R I K W 9 118 S D S D A S L V I 9 187 V I A S F D Q L Y 9
258 N G R F Y Y L I H 9 310 A D G S V R Y P I 9 345 Y G V Y C F R A
Y 9 24 L D H D R A I H I 8 134 Y G R Y K C E V I 8 136 R Y K C E V
I E G 8 154 L D L Q G V V F P 8 214 S V Q Y P I T K P 8 223 R E P C
G G Q N T 8 224 E P C G G Q N T V 8 254 T S N F N G R F Y 8 5 L L L
V L I S I C 7 66 D P T A F G S G I 7 78 R I K W T K L T S 7 99 G Y
H K K T Y G G 7 112 V F L K G G S D S 7 143 E G L E D D T V V 7 199
R G G L D W C N A 7 208 G W L S D G S V Q 7 251 F C F T S N F N G 7
257 F N G R F Y Y L I 7 287 A K V G Q I F A A 7 296 W K I L G Y D R
C 7 297 K I L G Y D R C D 7 303 R C D A G W L A D 7 313 S V R Y P I
S R P 7 3 S L L L L V L I S 6 7 L V L I S I C W A 6 30 I H I Q A E
N G P 6 37 G P H L L V E A E 6 38 P H L L V E A E Q 6 41 L V E A E
Q A K V 6 53 R G G N V T L P C 6 61 C K F Y R D P T A 6 79 I K W T
K L T S D 6 98 M G Y H K K T Y G 6 102 K K T Y G G Y Q G 6 104 T Y
G G Y Q G R V 6 113 F L K G G S D S D 6 140 E V I E G L E D D 6 152
V A L D L Q G V V 6 169 R Y N L N F H E A 6 172 L N F H E A Q Q A 6
189 A S F D Q L Y D A 6 192 D Q L Y D A W R G 6 197 A W R G G L D W
C 6 200 G G L D W C N A G 6 225 P C G G Q N T V P 6 238 Y G F W D K
D K S 6 270 L T Y D E A V Q A 6 274 E A V Q A C L N D 6 281 N D G A
Q I A K V 6 286 I A K V G Q I F A 6 288 K V G Q I F A A W 6 324 R C
S P T E A A V 6 346 G V Y C F R A Y N 6 6 L L V L I S I C W 5 15 A
D H L S D N Y T 5 34 A E N G P H L L V 5 39 H L L V E A E Q A 5 48
K V F S H R G G N 5 65 R D P T A F G S G 5 83 K L T S D Y L K E 5
86 S D Y L K E V D V 5 114 L K G G S D S D A 5 117 G S D S D A S L
V 5 124 L V I T D L T L E 5 131 L E D Y G R Y K C 5 142 I E G L E D
D T V 5 144 G L E D D T V V V 5 150 V V V A L D L Q G 5 201 G L D W
C N A G W 5 207 A G W L S D G S V 5 227 G G Q N T V P G V 5 247 R Y
D V F C F T S 5 265 I H P T K L T Y D 5 282 D G A Q I A K V G 5 283
G A Q I A K V G Q 5 294 A A W K I L G Y D 5 300 G Y D R C D A G W 5
320 R P R R R C S P T 5 8 V L I S I C W A D 4 29 A I H I Q A E N G
4 35 E N G P H L L V E 4 36 N G P H L L V E A 4 43 E A E Q A K V F
S 4 50 F S H R G G N V T 4 58 T L P C K F Y R D 4 74 I H K I R I K
W T 4 88 Y L K E V D V F V 4 96 V S M G Y H K K T 4 108 Y Q G R V F
L K G 4 120 S D A S L V I T D 4 122 A S L V I T D L T 4 132 E D Y G
R Y K C E 4 139 C E V I E G L E D 4 181 C L D Q D A V I A 4 188 I A
S F D Q L Y D 4 204 W C N A G W L S D 4 205 C N A G W L S D G 4 210
L S D G S V Q Y P 4 216 Q Y P I T K P R E 4 217 Y P I T K P R E P 4
221 K P R E P C G G Q 4 229 Q N T V P G V R N 4 231 T V P G V R N Y
G 4 242 D K D K S R Y D V 4 248 Y D V F C F T S N 4 266 H P T K L T
Y D E 4 269 K L T Y D E A V Q 4 304 C D A G W L A D G 4 306 A G W L
A D G S V 4 309 L A D G S V R Y P 4 338 P D K K H K L Y G 4 341 K H
K L Y G V Y C 4 12 I C W A D H L S D 3 21 N Y T L D H D R A 3 25 D
H D R A I H I Q 3 26 H D R A I H I Q A 3 46 Q A K V F S H R G 3 47
A K V F S H R G G 3 85 T S D Y L K E V D 3 115 K G G S D S D A S 3
119 D S D A S L V I T 3 125 V I T D L T L E D 3 127 T D L T L E D Y
G 3 138 K C E V I E G L E 3 141 V I E G L E D D T 3 145 L E D D T V
V V A 3 147 D D T V V V A L D 3 173 N F H E A Q Q A C 3 175 H E A Q
Q A C L D 3 176 E A Q Q A C L D Q 3 177 A Q Q A C L D Q D 3 179 Q A
C L D Q D A V 3 184 Q D A V I A S F D 3 190 S F D Q L Y D A W 3 196
D A W R G G L D W 3 218 P I T K P R E P C 3 219 I T K P R E P C G 3
226 C G G Q N T V P G 3 234 G V R N Y G F W D 3 263 Y L I H P T K L
T 3 268 T K L T Y D E A V 3 275 A V Q A C L N D G 3 279 C L N D G A
Q I A 3 292 I F A A W K I L G 3 317 P I S R P R R R C 3 330 A A V R
F V G F P 3 339 D K K H K L Y G V 3 13 C W A D H L S D N 2 17 H L S
D N Y T L D 2 49 V F S H R G G N V 2 59 L P C K F Y R D P 2 63 F Y
R D P T A F G 2 84 L T S D Y L K E V 2 89 L K E V D V F V S 2 91 E
V D V F V S M G 2 133 D Y G R Y K C E V 2 149 T V V V A L D L Q 2
151 V V A L D L Q G V 2 157 Q G V V F P Y F P 2 170 Y N L N F H E A
Q 2 171 N L N F H E A Q Q 2 178 Q Q A C L D Q D A 2 182 L D Q D A V
I A S 2 185 D A V I A S F D Q 2 193 Q L Y D A W R G G 2 206 N A G W
L S D G S 2 241 W D K D K S R Y D 2 244 D K S R Y D V F C 2 250 V F
C F T S N F N 2 267 P T K L T Y D E A 2 271 T Y D E A V Q A C 2 276
V Q A C L N D G A 2 277 Q A C L N D G A Q 2 299 L G Y D R C D A G 2
305 D A G W L A D G S 2 318 I S R P R R R C S 2 328 T E A A V R F V
G 2 331 A V R F V G F P D 2 344 L Y G V Y C F R A 2 11 S I C W A D
H L S 1 19 S D N Y T L D H D 1 109 Q G R V F L K G G 1 163 Y F P R
L G R Y N 1 203 D W C N A G W L S 1 212 D G S V Q Y P I T 1 220 T K
P R E P C G G 1 233 P G V R N Y G F W 1 273 D E A V Q A C L N 1 298
I L G Y D R C D A 1 311 D G S V R Y P I S 1 327 P T E A A V R F V 1
151P3D4 v.2: HLA Peptide Scoring Results B*2705 9-mers SYFPEITHI
203 M R L Q K Q A E K 29 120 K R M N T N P S R 25 258 P R A G S S A
H R 25 196 Y R K N K Q L M R 24 229 P R G L G F I F K 24 248 T R I
G H P G G R 24 137 S R I F W R Q E K 23 187 K R K E K A E I H 23
265 H R P P A L S A R 23 312 P R N P L P N P R 23 21 I R D H S G Q
K M 22 333 A R H C Q G Q K H 21 197 R K N K Q L M R L 20 398 E R K
A E N G P H 20 57 V Q F V G S Y K L 19 83 R K D K V L L G R 19 234
F I F K T I A P L 19 251 G H P G G R T P R 19 327 G G L K K P A R H
19 22 R D H S G Q K M K 18 26 G Q K M K Q D K K 18 155 G H A S E A
Y K K 18 207 K Q A E K N M K K 18 313 R N P L P N P R H 18 345 A R
G K P Q R K P 18 389 G L G G K Q K D K 18 391 G G K Q K D K E R 18
392 G K Q K D K E R K 18 34 K V D L L V P T K 17 90 G R K A V V V S
C 17 105 G S F C R N K L K 17 109 R N K L K Y L A F 17 113 K Y L A
F L H K R 17 121 R M N T N P S R R 17 211 K N M K K K I D K 17 323
P S G G G G L K K 17 326 G G G L K K P A R 17 378 A L W K A I E S L
17 7 K T F P L R A L H 16 11 L R A L H I V V E 16 30 K Q D K K V D
L L 16 46 I I T Q G A K D F 16 55 G H V Q F V G S Y 16 81 K Q R K D
K V L L 16 84 K D K V L L G R K 16 101 I N I S G S F C R 16 110 N K
L K Y L A F L 16 189 K E K A E I H Y R 16 194 I H Y R K N K Q L 16
212 N M K K K I D K Y 16 255 G R T P R A G S S 16 308 S P Y G P R N
P L 16 373 S G Y C G A L W K 16 399 R K A E N G P H L 16 16 I V V E
S I R D H 15 51 A K D F G H V Q F 15 75 T V Y Q D E K Q R 15 99 E G
I N I S G S F 15 108 C R N K L K Y L A 15 128 R R P Y H F Q V P 15
131 Y H F Q V P S R I 15 168 G A P H E V G W K 15 176 K Y Q A V T A
T L 15 188 R K E K A E I H Y 15 190 E K A E I H Y R K 15 192 A E I
H Y R K N K 15 222 E S P G G G S P R 15 226 G G S P R G L G F 15
238 T I A P L A A T R 15 336 C Q G Q K H N V L 15 338 G Q K H N V L
A R 15 343 V L A R G K P Q R 15 344 L A R G K P Q R K 15 346 R G K
P Q R K P K 15 350 Q R K P K S E N N 15 365 G R P A D L A G S 15 14
L H I V V E S I R 14 44 T G I I T Q G A K 14 76 V Y Q D E K Q R K
14 112 L K Y L A F L H K 14 169 A P H E V G W K Y 14 181 T A T L E
E K R K 14 208 Q A E K N M K K K 14 272 A R A P V P A A S 14 285 L
P L R T P W T R 14 322 S P S G G G G L K 14 340 K H N V L A R G K
14 385 S L E E G L G G K 14 387 E E G L G G K Q K 14 400 K A E N G
P H L L 14 4 H T T K T F P L R 13 25 S G Q K M K Q D K 13 29 M K Q
D K K V D L 13 73 H W T V Y Q D E K 13 80 E K Q R K D K V L 13 82 Q
R K D K V L L G 13 103 I S G S F C R N K 13 104 S G S F C R N K L
13 130 P Y H F Q V P S R 13 134 Q V P S R I F W R 13 141 W R Q E K
A D G G 13 158 S E A Y K K V C L 13 163 K V C L S G A P H 13 179 A
V T A T L E E K 13 180 V T A T L E E K R 13 183 T L E E K R K E K
13 199 N K Q L M R L Q K 13 206 Q K Q A E K N M K 13 224 P G G G S
P R G L 13 228 S P R G L G F I F 13 230 R G L G F I F K T 13 245 T
R A T R I G H P 13 277 P A A S P A A W L 13 292 T R P S S C P T S
13 302 S T Y D S L S P Y 13 305 D S L S P Y G P R 13 332 P A R H C
Q G Q K 13 362 V E N G R P A D L 13 371 A G S G Y C G A L 13 6 T K
T F P L R A L 12 20 S I R D H S G Q K 12 56 H V Q F V G S Y K 12 65
L A Y S N D G E H 12 69 N D G E H W T V Y 12 78 Q D E K Q R K D K
12 106 S F C R N K L K Y 12 107 F C R N K L K Y L 12 111 K L K Y L
A F L H 12 127 S R R P Y H F Q V 12 132 H F Q V P S R I F 12 154 Q
G H A S E A Y K 12 186 E K R K E K A E I 12 205 L Q K Q A E K N M
12 227 G S P R G L G F I 12 241 P L A A T R A T R 12 257 T P R A G
S S A H 12 279 A S P A A W L P L 12 280 S P A A W L P L R 12 296 S
C P T S S S T Y 12 319 P R H S P S G G G 12 321 H S P S G G G G L
12 358 N S W Y V E N G R 12 382 A I E S L E E G L 12 1 M L E H T T
K T F 11 3 E H T T K T F P L 11 42 K V T G I I T Q G 11 61 G S Y K
L A Y S N 11 114 Y L A F L H K R M 11 125 N P S R R P Y H F 11 138
R I F W R Q E K A 11 148 G G S C C P Q G H 11 195 H Y R K N K Q L M
11 231 G L G F I F K T I 11 242 L A A T R A T R I 11 262 S S A H R
P P A L 11 287 L R T P W T R P S 11 299 T S S S T Y D S L 11 353 P
K S E N N S W Y 11 12 R A L H I V V E S 10 13 A L H I V V E S I 10
38 L V P T K V T G I 10 48 T Q G A K D F G H 10 59 F V G S Y K L A
Y 10 95 V V S C E G I N I 10 123 N T N P S R R P Y 10 209 A E K N M
K K K I 10 244 A T R A T R I G H 10 334 R H C Q G Q K H N 10 351 R
K P K S E N N S 10 367 P A D L A G S G Y 10 8 T F P L R A L H I 9
39 V P T K V T G I I 9 93 A V V V S C E G I 9 124 T N P S R R P Y H
9 129 R P Y H F Q V P S 9 153 P Q G H A S E A Y 9 204 R L Q K Q A E
K N 9 266 R P P A L S A R A 9 347 G K P Q R K P K S 9 374 G Y C G A
L W K A 9 377 G A L W K A I E S 9 388 E G L G G K Q K D 9 35 V D L
L V P T K V 8 41 T K V T G I I T Q 8 45 G I I T Q G A K D 8 52 K D
F G H V Q F V 8 182 A T L E E K R K E 8 215 K K I D K Y T E S 8 223
S P G G G S P R G 8 259 R A G S S A H R P 8 273 R A P V P A A S P 8
311 G P R N P L P N P 8 381 K A I E S L E E G 8 86 K V L L G R K A
V 7 87 V L L G R K A V V 7 91 R K A V V V S C E 7 96 V S C E G I N
I S 7 116 A F L H K R M N T 7 142 R Q E K A D G G S 7 145 K A D G G
S C C P 7 175 W K Y Q A V T A T 7 200 K Q L M R L Q K Q 7 233 G F I
F K T I A P 7 237 K T I A P L A A T 7 239 I A P L A A T R A 7 249 R
I G H P G G R T 7 283 A W L P L R T P W 7 293 R P S S C P T S S 7
324 S G G G G L K K P 7 325 G G G G L K K P A 7 328 G L K K P A R H
C 7 366 R P A D L A G S G 7 375 Y C G A L W K A I 7 15 H I V V E S
I R D 6 23 D H S G Q K M K Q 6 28 K M K Q D K K V D 6 33 K K V D L
L V P T 6 71 G E H W T V Y Q D 6 77 Y Q D E K Q R K D 6 92 K A V V
V S C E G 6 97 S C E G I N I S G 6 149 G S C C P Q G H A 6 151 C C
P Q G H A S E 6 159 E A Y K K V C L S 6 160 A Y K K V C L S G 6 164
V C L S G A P H E 6 171 H E V G W K Y Q A 6 173 V G W K Y Q A V T 6
174 G W K Y Q A V T A 6 232 L G F I F K T I A 6 256 R T P R A G S S
A 6 264 A H R P P A L S A 6 288 R T P W T R P S S 6 320 R H S P S G
G G G 6 349 P Q R K P K S E N 6 352 K P K S E N N S W 6 359 S W Y V
E N G R P 6 368 A D L A G S G Y C 6 395 K D K E R K A E N 6 27 Q K
M K Q D K K V 5 31 Q D K K V D L L V 5 37 L L
V P T K V T G 5 68 S N D G E H W T V 5 79 D E K Q R K D K V 5 85 D
K V L L G R K A 5 89 L G R K A V V V S 5 100 G I N I S G S F C 5
102 N I S G S F C R N 5 115 L A F L H K R M N 5 118 L H K R M N T N
P 5 140 F W R Q E K A D G 5 152 C P Q G H A S E A 5 162 K K V C L S
G A P 5 184 L E E K R K E K A 5 198 K N K Q L M R L Q 5 214 K K K I
D K Y T E 5 216 K I D K Y T E S P 5 218 D K Y T E S P G G 5 246 R A
T R I G H P G 5 250 I G H P G G R T P 5 252 H P G G R T P R A 5 254
G G R T P R A G S 5 274 A P V P A A S P A 5 282 A A W L P L R T P 5
286 P L R T P W T R P 5 335 H C Q G Q K H N V 5 339 Q K H N V L A R
G 5 384 E S L E E G L G G 5 386 L E E G L G G K Q 5 390 L G G K Q K
D K E 5 393 K Q K D K E R K A 5 397 K E R K A E N G P 5 24 H S G Q
K M K Q D 4 36 D L L V P T K V T 4 47 I T Q G A K D F G 4 50 G A K
D F G H V Q 4 53 D F G H V Q F V G 4 58 Q F V G S Y K L A 4 62 S Y
K L A Y S N D 4 63 Y K L A Y S N D G 4 64 K L A Y S N D G E 4 74 W
T V Y Q D E K Q 4 88 L L G R K A V V V 4 98 C E G I N I S G S 4 117
F L H K R M N T N 4 122 M N T N P S R R P 4 133 F Q V P S R I F W 4
135 V P S R I F W R Q 4 146 A D G G S C C P Q 4 191 K A E I H Y R K
N 4 193 E I H Y R K N K Q 4 201 Q L M R L Q K Q A 4 213 M K K K I D
K Y T 4 219 K Y T E S P G G G 4 221 T E S P G G G S P 4 225 G G G S
P R G L G 4 235 I F K T I A P L A 4 247 A T R I G H P G G 4 261 G S
S A H R P P A 4 269 A L S A R A P V P 4 278 A A S P A A W L P 4 281
P A A W L P L R T 4 295 S S C P T S S S T 4 297 C P T S S S T Y D 4
306 S L S P Y G P R N 4 307 L S P Y G P R N P 4 337 Q G Q K H N V L
A 4 341 H N V L A R G K P 4 348 K P Q R K P K S E 4 354 K S E N N S
W Y V 4 369 D L A G S G Y C G 4 372 G S G Y C G A L W 4 380 W K A I
E S L E E 4 396 D K E R K A E N G 4 2 L E H T T K T F P 3 5 T T K T
F P L R A 3 9 F P L R A L H I V 3 10 P L R A L H I V V 3 19 E S I R
D H S G Q 3 32 D K K V D L L V P 3 60 V G S Y K L A Y S 3 144 E K A
D G G S C C 3 156 H A S E A Y K K V 3 157 A S E A Y K K V C 3 165 C
L S G A P H E V 3 177 Y Q A V T A T L E 3 178 Q A V T A T L E E 3
240 A P L A A T R A T 3 267 P P A L S A R A P 3 268 P A L S A R A P
V 3 271 S A R A P V P A A 3 290 P W T R P S S C P 3 291 W T R P S S
C P T 3 294 P S S C P T S S S 3 301 S S T Y D S L S P 3 303 T Y D S
L S P Y G 3 304 Y D S L S P Y G P 3 309 P Y G P R N P L P 3 314 N P
L P N P R H S 3 317 P N P R H S P S G 3 330 K K P A R H C Q G 3 355
S E N N S W Y V E 3 357 N N S W Y V E N G 3 361 Y V E N G R P A D 3
364 N G R P A D L A G 3 376 C G A L W K A I E 3 383 I E S L E E G L
G 3 394 Q K D K E R K A E 3 18 V E S I R D H S G 2 49 Q G A K D F G
H V 2 67 Y S N D G E H W T 2 147 D G G S C C P Q G 2 161 Y K K V C
L S G A 2 166 L S G A P H E V G 2 167 S G A P H E V G W 2 170 P H E
V G W K Y Q 2 202 L M R L Q K Q A E 2 210 E K N M K K K I D 2 217 I
D K Y T E S P G 2 263 S A H R P P A L S 2 275 P V P A A S P A A 2
276 V P A A S P A A W 2 284 W L P L R T P W T 2 289 T P W T R P S S
C 2 298 P T S S S T Y D S 2 300 S S S T Y D S L S 2 315 P L P N P R
H S P 2 316 L P N P R H S P S 2 318 N P R H S P S G G 2 331 K P A R
H C Q G Q 2 342 N V L A R G K P Q 2 356 E N N S W Y V E N 2 360 W Y
V E N G R P A 2 363 E N G R P A D L A 2 370 L A G S G Y C G A 2 379
L W K A I E S L E 2 17 V V E S I R D H S 1 40 P T K V T G I I T 1
43 V T G I I T Q G A 1 54 F G H V Q F V G S 1 66 A Y S N D G E H W
1 70 D G E H W T V Y Q 1 72 E H W T V Y Q D E 1 94 V V V S C E G I
N 1 119 H K R M N T N P S 1 126 P S R R P Y H F Q 1 136 P S R I F W
R Q E 1 139 I F W R Q E K A D 1 143 Q E K A D G G S C 1 150 S C C P
Q G H A S 1 172 E V G W K Y Q A V 1 185 E E K R K E K A E 1 220 Y T
E S P G G G S 1 236 F K T I A P L A A 1 243 A A T R A T R I G 1 260
A G S S A H R P P 1 270 L S A R A P V P A 1 310 Y G P R N P L P N 1
329 L K K P A R H C Q 1
[0832]
39TABLE XXXII SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P364 v.1:
HLA Peptide Scoring Results B*2709 9-mers SYFPEITHI 106 G G Y Q G R
V F L 16 135 G R Y K C E V I E 16 16 D H L S D N Y T L 15 159 V V F
P Y F P R L 15 168 G R Y N L N F H E 15 259 G R F Y Y L I H P 15
323 R R C S P T E A A 15 110 G R V F L K G G S 14 117 G S D S D A S
L V 14 166 R L G R Y N L N F 14 314 V R Y P I S R P R 14 322 R R R
C S P T E A 14 2 K S L L L L V L I 13 10 I S I C W A D H L 13 62 K
F Y R D P T A F 13 116 G G S D S D A S L 13 144 G L E D D T V V V
13 148 D T V V V A L D L 13 186 A V I A S F D Q L 13 227 G G Q N T
V P G V 13 278 A C L N D G A Q I 13 290 G Q I F A A W K I 13 324 R
C S P T E A A V 13 332 V R F V G F P D K 13 336 G F P D K K H K L
13 32 I Q A E N G P H L 12 55 G N V T L P C K F 12 64 Y R D P T A F
G S 12 71 G S G I H K I R I 12 76 K I R I K W T K L 12 77 I R I K W
T K L T 12 90 K E V D V F V S M 12 123 S L V I T D L T L 12 146 E D
D T V V V A L 12 164 F P R L G R Y N L 12 165 P R L G R Y N L N 12
222 P R E P C G G Q N 12 245 K S R Y D V F C F 12 246 S R Y D V F C
F T 12 262 Y Y L I H P T K L 12 284 A Q I A K V G Q I 12 291 Q I F
A A W K I L 12 301 Y D R C D A G W L 12 326 S P T E A A V R F 12
342 H K L Y G V Y C F 12 1 M K S L L L L V L 11 51 S H R G G N V T
L 11 52 H R G G N V T L P 11 86 S D Y L K E V D V 11 87 D Y L K E V
D V F 11 143 E G L E D D T V V 11 180 A C L D Q D A V I 11 202 L D
W C N A G W L 11 243 K D K S R Y D V F 11 249 D V F C F T S N F 11
256 N F N G R F Y Y L 11 310 A D G S V R Y P I 11 321 P R R R C S P
T E 11 4 L L L L V L I S I 10 22 Y T L D H D R A I 10 27 D R A I H
I Q A E 10 33 Q A E N G P H L L 10 34 A E N G P H L L V 10 69 A F G
S G I H K I 10 81 W T K L T S D Y L 10 121 D A S L V I T D L 10 137
Y K C E V I E G L 10 152 V A L D L Q G V V 10 153 A L D L Q G V V F
10 174 F H E A Q Q A C L 10 194 L Y D A W R G G L 10 198 W R G G L
D W C N 10 211 S D G S V Q Y P I 10 235 V R N Y G F W D K 10 268 T
K L T Y D E A V 10 272 Y D E A V Q A C L 10 302 D R C D A G W L A
10 319 S R P R R R C S P 10 24 L D H D R A I H I 9 42 V E A E Q A K
V F 9 49 V F S H R G G N V 9 66 D P T A F G S G I 9 88 Y L K E V D
V F V 9 104 T Y G G Y Q G R V 9 118 S D S D A S L V I 9 142 I E G L
E D D T V 9 151 V V A L D L Q G V 9 156 L Q G V V F P Y F 9 179 Q A
C L D Q D A V 9 207 A G W L S D G S V 9 232 V P G V R N Y G F 9 242
D K D K S R Y D V 9 253 F T S N F N G R F 9 257 F N G R F Y Y L I 9
306 A G W L A D G S V 9 327 P T E A A V R F V 9 329 E A A V R F V G
F 9 339 D K K H K L Y G V 9 41 L V E A E Q A K V 8 84 L T S D Y L K
E V 8 105 Y G G Y Q G R V F 8 133 D Y G R Y K C E V 8 134 Y G R Y K
C E V I 8 183 D Q D A V I A S F 8 224 E P C G G Q N T V 8 281 N D G
A Q I A K V 8 285 Q I A K V G Q I F 8 208 G W L S D G S V Q 7 28 R
A I H I Q A E N 6 83 K L T S D Y L K E 6 111 R V F L K G G S D 6
199 R G G L D W C N A 6 236 R N Y G F W D K D 6 260 R F Y Y L I H P
T 6 307 G W L A D G S V R 6 315 R Y P I S R P R R 6 48 K V F S H R
G G N 5 53 R G G N V T L P C 5 78 R I K W T K L T S 5 102 K K T Y G
G Y Q G 5 136 R Y K C E V I E G 5 192 D Q L Y D A W R G 5 200 G G L
D W C N A G 5 223 R E P C G G Q N T 5 270 L T Y D E A V Q A 5 303 R
C D A G W L A D 5 333 R F V G F P D K K 5 346 G V Y C F R A Y N 5 3
S L L L L V L I S 4 37 G P H L L V E A E 4 39 H L L V E A E Q A 4
54 G G N V T L P C K 4 65 R D P T A F G S G 4 73 G I H K I R I K W
4 99 G Y H K K T Y G G 4 103 K T Y G G Y Q G R 4 107 G Y Q G R V F
L K 4 115 K G G S D S D A S 4 122 A S L V I T D L T 4 129 L T L E D
Y G R Y 4 154 L D L Q G V V F P 4 158 G V V F P Y F P R 4 162 P Y F
P R L G R Y 4 169 R Y N L N F H E A 4 172 L N F H E A Q Q A 4 189 A
S F D Q L Y D A 4 213 G S V Q Y P I T K 4 215 V Q Y P I T K P R 4
230 N T V P G V R N Y 4 247 R Y D V F C F T S 4 261 F Y Y L I H P T
K 4 269 K L T Y D E A V Q 4 283 G A Q I A K V G Q 4 297 K I L G Y D
R C D 4 312 G S V R Y P I S R 4 320 R P R R R C S P T 4 335 V G F P
D K K H K 4 343 K L Y G V Y C F R 4 8 V L I S I C W A D 3 12 I C W
A D H L S D 3 21 N Y T L D H D R A 3 29 A I H I Q A E N G 3 57 V T
L P C K F Y R 3 61 C K F Y R D P T A 3 80 K W T K L T S D Y 3 82 T
K L T S D Y L K 3 94 V F V S M G Y H K 3 138 K C E V I E G L E 3
150 V V V A L D L Q G 3 161 F P Y F P R L G R 3 181 C L D Q D A V I
A 3 188 I A S F D Q L Y D 3 201 G L D W C N A G W 3 219 I T K P R E
P C G 3 228 G Q N T V P G V R 3 229 Q N T V P G V R N 3 234 G V R N
Y G F W D 3 238 Y G F W D K D K S 3 239 G F W D K D K S R 3 251 F C
F T S N F N G 3 274 E A V Q A C L N D 3 288 K V G Q I F A A W 3 300
G Y D R C D A G W 3 316 Y P I S R P R R R 3 330 A A V R F V G F P 3
341 K H K L Y G V Y C 3 5 L L L V L I S I C 2 6 L L V L I S I C W 2
7 L V L I S I C W A 2 20 D N Y T L D H D R 2 26 H D R A I H I Q A 2
30 I H I Q A E N G P 2 35 E N G P H L L V E 2 38 P H L L V E A E Q
2 44 A E Q A K V F S H 2 47 A K V F S H R G G 2 58 T L P C K F Y R
D 2 68 T A F G S G I H K 2 75 H K I R I K W T K 2 89 L K E V D V F
V S 2 93 D V F V S M G Y H 2 98 M G Y H K K T Y G 2 112 V F L K G G
S D S 2 120 S D A S L V I T D 2 124 L V I T D L T L E 2 125 V I T D
L T L E D 2 127 T D L T L E D Y G 2 128 D L T L E D Y G R 2 132 E D
Y G R Y K C E 2 139 C E V I E G L E D 2 145 L E D D T V V V A 2 147
D D T V V V A L D 2 157 Q G V V F P Y F P 2 170 Y N L N F H E A Q 2
177 A Q Q A C L D Q D 2 184 Q D A V I A S F D 2 193 Q L Y D A W R G
G 2 209 W L S D G S V Q Y 2 216 Q Y P I T K P R E 2 221 K P R E P C
G G Q 2 240 F W D K D K S R Y 2 252 C F T S N F N G R 2 255 S N F N
G R F Y Y 2 264 L I H P T K L T Y 2 266 H P T K L T Y D E 2 282 D G
A Q I A K V G 2 287 A K V G Q I F A A 2 294 A A W K I L G Y D 2 295
A W K I L G Y D R 2 296 W K I L G Y D R C 2 298 I L G Y D R C D A 2
299 L G Y D R C D A G 2 308 W L A D G S V R Y 2 318 I S R P R R R C
S 2 340 K K H K L Y G V Y 2 14 W A D H L S D N Y 1 15 A D H L S D N
Y T 1 18 L S D N Y T L D H 1 23 T L D H D R A I H 1 36 N G P H L L
V E A 1 40 L L V E A E Q A K 1 43 E A E Q A K V F S 1 46 Q A K V F
S H R G 1 56 N V T L P C K F Y 1 70 F G S G I H K I R 1 72 S G I H
K I R I K 1 74 I H K I R I K W T 1 79 I K W T K L T S D 1 91 E V D
V F V S M G 1 92 V D V F V S M G Y 1 108 Y Q G R V F L K G 1 119 D
S D A S L V I T 1 126 I T D L T L E D Y 1 131 L E D Y G R Y K C 1
140 E V I E G L E D D 1 149 T V V V A L D L Q 1 155 D L Q G V V F P
Y 1 171 N L N F H E A Q Q 1 175 H E A Q Q A C L D 1 176 E A Q Q A C
L D Q 1 182 L D Q D A V I A S 1 185 D A V I A S F D Q 1 187 V I A S
F D Q L Y 1 196 D A W R G G L D W 1 197 A W R G G L D W C 1 204 W C
N A G W L S D 1 210 L S D G S V Q Y P 1 212 D G S V Q Y P I T 1 217
Y P I T K P R E P 1 218 P I T K P R E P C 1 226 C G G Q N T V P G 1
233 P G V R N Y G F W 1 244 D K S R Y D V F C 1 248 Y D V F C F T S
N 1 258 N G R F Y Y L I H 1 263 Y L I H P T K L T 1 265 I H P T K L
T Y D 1 271 T Y D E A V Q A C 1 273 D E A V Q A C L N 1 275 A V Q A
C L N D G 1 279 C L N D G A Q I A 1 286 I A K V G Q I F A 1 289 V G
Q I F A A W K 1 292 I F A A W K I L G 1 293 F A A W K I L G Y 1 305
D A G W L A D G S 1 309 L A D G S V R Y P 1 311 D G S V R Y P I S 1
313 S V R Y P I S R P 1 317 P I S R P R R R C 1 325 C S P T E A A V
R 1 331 A V R F V G F P D 1 338 P D K K H K L Y G 1 344 L Y G V Y C
F R A 1 345 Y G V Y C F R A Y 1 151P3D4 v.2: HLA Peptide Scoring
Results B*2709 9-mers SYFPEITHI 127 S R R P Y H F Q V 20 21 I R D H
S G Q K M 19 255 G R T P R A G S S 16 90 G R K A V V V S C 15 197 R
K N K Q L M R L 15 399 R K A E N G P H L 15 81 K Q R K D K V L L 14
128 R R P Y H F Q V P 14 194 I H Y R K N K Q L 14 365 G R P A D L A
G S 14 30 K Q D K K V D L L 13 52 K D F G H V Q F V 13 57 V Q F V G
S Y K L 13 109 R N K L K Y L A F 13 120 K R M N T N P S R 13 187 K
R K E K A E I H 13 226 G G S P R G L G F 13 82 Q R K D K V L L G 12
86 K V L L G R K A V 12 110 N K L K Y L A F L 12 176 K Y Q A V T A
T L 12 203 M R L Q K Q A E K 12 231 G L G F I F K T I 12 234 F I F
K T I A P L 12 272 A R A P V P A A S 12 277 P A A S P A A W L 12
279 A S P A A W L P L 12 287 L R T P W T R P S 12 292 T R P S S C P
T S 12 308 S P Y G P R N P L 12 350 Q R K P K S E N N 12 382 A I E
S L E E G L 12 400 K A E N G P H L L 12 3 E H T T K T F P L 11 6 T
K T F P L R A L 11 11 L R A L H I V V E 11 29 M K Q D K K V D L 11
46 I I T Q G A K D F 11 51 A K D F G H V Q F 11 108 C R N K L K Y L
A 11 131 Y H F Q V P S R I 11 137 S R I F W R Q E K 11 141 W R Q E
K A D G G 11 158 S E A Y K K V C L 11 196 Y R K N K Q L M R 11 227
G S P R G L G F I 11 248 T R I G H P G G R 11 262 S S A H R P P A L
11 265 H R P P A L S A R 11 268 P A L S A R A P V 11 299 T S S S T
Y D S L 11 312 P R N P L P N P R 11 319 P R H S P S G G G 11 321 H
S P S G G G G L 11 333 A R H C Q G Q K H 11 345 A R G K P Q R K P
11 371 A G S G Y C G A L 11 378 A L W K A I E S L 11 8 T F P L R A
L H I 10 9 F P L R A L H I V 10 13 A L H I V V E S I 10 35 V D L L
V P T K V 10 80 E K Q R K D K V L 10 87 V L L G R K A V V 10 88 L L
G R K A V V V 10 93 A V V V S C E G I 10 99 E G I N I S G S F 10
104 S G S F C R N K L 10 107 F C R N K L K Y L 10 224 P G G G S P R
G L 10 229 P R G L G F I F K 10 242 L A A T R A T R I 10 245 T R A
T R I G H P 10 258 P R A G S S A H R 10 336 C Q G Q K H N V L 10
354 K S E N N S W Y V 10 362 V E N G R P A D L 10 398 E R K A E N G
P H 10 12 R A L H I V V E S 9 31 Q D K K V D L L V 9 38 L V P T K V
T G I 9 39 V P T K V T G I I 9 49 Q G A K D F G H V 9 95 V V S C E
G I N I 9 114 Y L A F L H K R M 9 125 N P S R R P Y H F 9 205 L Q K
Q A E K N M 9 209 A E K N M K K K I 9 335 H C Q G Q K H N V 9 1 M L
E H T T K T F 8 10 P L R A L H I V V 8 27 Q K M K Q D K K V 8 68 S
N D G E H W T V 8 79 D E K Q R K D K V 8 132 H F Q V P S R I F 8
156 H A S E A Y K K V 8 165 C L S G A P H E V 8 172 E V G W K Y Q A
V 8 186 E K R K E K A E I 8 195 H Y R K N K Q L M 8 228 S P R G L G
F I F 8 375 Y C G A L W K A I 8 61 G S Y K L A Y S N 7 129 R P Y H
F Q V P S 7 259 R A G S S A H R P 7 71 G E H W T V Y Q D 6 138 R I
F W R Q E K A 6 155 G H A S E A Y K K 6 230 R G L G F I F K T 6 246
R A T R I G H P G 6 313 R N P L P N P R H 6 327 G G L K K P A R H 6
377 G A L W K A I E S 6 7 K T F P L R A L H 5 22 R D H S G Q K M K
5 42 K V T G I I T Q G 5 55 G H V Q F V G S Y 5 83 R K D K V L L G
R 5 91 R K A V V V S C E 5 105 G S F C R N K L K 5 121 R M N T N P
S R R 5 164 V C L S G A P H E 5 174 G W K Y Q A V T A 5 204 R L Q K
Q A E K N 5 249 R I G H P G G R T 5 266 R P P A L S A R A 5 273 R A
P V P A A S P 5 288 R T P W T R P S S 5 293 R P S S C P T S S 5 311
G P R N P L P N P 5 320 R H S P S G G G G 5 338 G Q K H N V L A R 5
346 R G K P Q R K P K 5 351 R K P K S E N N S 5 366 R P A D L A G S
G 5 392 G K Q K D K E R K 5 33 K K V D L L V P T 4 34 K V D L L V P
T K 4 45 G I I T Q G A K D 4 75 T V Y Q D E K Q R 4 113 K Y L A F L
H K R 4 116 A F L H K R M N T 4 142 R Q E K A D G G S 4 168 G A P H
E V G W K 4 188 R K E K A E I H Y 4 200 K Q L M R L Q K Q 4 214 K K
K I D K Y T E 4 225 G G G S P R G L G 4 233 G F I F K T I A P 4 235
I F K T I A P L A 4 256 R T P R A G S S A 4 261 G S S A H R P P A 4
264 A H R P P A L S A 4 274 A P V P A A S P A 4 283 A W L P L R T P
W 4 326 G G G L K K P A R 4 328 G L K K P A R H C 4 334 R H C Q G Q
K H N 4 347 G K P Q R K P K S 4 373 S G Y C G A L W K 4 26 G Q K M
K Q D K K 3 28 K M K Q D K K V D 3 37 L L V P T K V T G 3 50 G A K
D F G H V Q 3 65 L A Y S N D G E H 3 84 K D K V L L G R K 3 92 K A
V V V S C E G 3 100 G I N I S G S F C 3 101 I N I S G S F C R 3 103
I S G S F C R N K 3 111 K L K Y L A F L H 3 112 L K Y L A F L H K 3
147 D G G S C C P Q G 3 148 G G S C C P Q G H 3 149 G S C C P Q G H
A 3 159 E A Y K K V C L S 3 162 K K V C L S G A P 3 171 H E V G W K
Y Q A 3 175 W K Y Q A V T A T 3 182 A T L E E K R K E 3 190 E K A E
I H Y R K 3 192 A E I H Y R K N K 3 215 K K I D K Y T E S 3 218 D K
Y T E S P G G 3 219 K Y T E S P G G G 3 237 K T I A P L A A T 3 239
I A P L A A T R A 3 240 A P L A A T R A T 3 251 G H P G G R T P R 3
254 G G R T P R A G S 3 269 A L S A R A P V P 3 278 A A S P A A W L
P 3 301 S S T Y D S L S P 3 305 D S L S P Y G P R 3 306 S L S P Y G
P R N 3 314 N P L P N P R H S 3 325 G G G G L K K P A 3 330 K K P A
R H C Q G 3 340 K H N V L A R G K 3 352 K P K S E N N S W 3 359 S W
Y V E N G R P 3 368 A D L A G S G Y C 3 372 G S G Y C G A L W 3 374
G Y C G A L W K A 3 381 K A I E S L E E G 3 384 E S L E E G L G G 3
389 G L G G K Q K D K 3 391 G G K Q K D K E R 3 4 H T T K T F P L R
2 5 T T K T F P L R A 2 15 H I V V E S I R D 2 16 I V V E S I R D H
2 17 V V E S I R D H S 2 19 E S I R D H S G Q 2 32 D K K V D L L V
P 2 36 D L L V P T K V T 2 59 F V G S Y K L A Y 2 63 Y K L A Y S N
D G 2 64 K L A Y S N D G E 2 66 A Y S N D G E H W 2 89 L G R K A V
V V S 2 94 V V V S C E G I N 2 115 L A F L H K R M N 2 122 M N T N
P S R R P 2 124 T N P S R R P Y H 2 130 P Y H F Q V P S R 2 133 F Q
V P S R I F W 2 135 V P S R I F W R Q 2 145 K A D G G S C C P 2 160
A Y K K V C L S G 2 163 K V C L S G A P H 2 167 S G A P H E V G W 2
178 Q A V T A T L E E 2 179 A V T A T L E E K 2 181 T A T L E E K R
K 2 189 K E K A E I H Y R 2 191 K A E I H Y R K N 2 198 K N K Q L M
R L Q 2 199 N K Q L M R L Q K 2 207 K Q A E K N M K K 2 211 K N M K
K K I D K 2 216 K I D K Y T E S P 2 223 S P G G G S P R G 2 232 L G
F I F K T I A 2 236 F K T I A P L A A 2 238 T I A P L A A T R 2 243
A A T R A T R I G 2 247 A T R I G H P G G 2 250 I G H P G G R T P 2
252 H P G G R T P R A 2 260 A G S S A H R P P 2 271 S A R A P V P A
A 2 281 P A A W L P L R T 2 285 L P L R T P W T R 2 297 C P T S S S
T Y D 2 298 P T S S S T Y D S 2 302 S T Y D S L S P Y 2 303 T Y D S
L S P Y G 2 309 P Y G P R N P L P 2 331 K P A R H C Q G Q 2 342 N V
L A R G K P Q 2 343 V L A R G K P Q R 2 348 K P Q R K P K S E 2 356
E N N S W Y V E N 2 357 N N S W Y V E N G 2 364 N G R P A D L A G 2
388 E G L G G K Q K D 2 393 K Q K D K E R K A 2 395 K D K E R K A E
N 2 396 D K E R K A E N G 2 397 K E R K A E N G P 2 14 L H I V V E
S I R 1 20 S I R D H S G Q K 1 24 H S G Q K M K Q D 1 41 T K V T G
I I T Q 1 43 V T G I I T Q G A 1 44 T G I I T Q G A K 1 47 I T Q G
A K D F G 1 54 F G H V Q F V G S 1 58 Q F V G S Y K L A 1 62 S Y K
L A Y S N D 1 70 D G E H W T V Y Q 1 73 H W T V Y Q D E K 1 74 W T
V Y Q D E K Q 1 76 V Y Q D E K Q R K 1 85 D K V L L G R K A 1 97 S
C E G I N I S G 1 102 N I S G S F C R N 1 106 S F C R N K L K Y 1
118 L H K R M N T N P 1 123 N T N P S R R P Y 1 134 Q V P S R I F W
R 1 136 P S R I F W R Q E 1
139 I F W R Q E K A D 1 143 Q E K A D G G S C 1 146 A D G G S C C P
Q 1 150 S C C P Q G H A S 1 152 C P Q G H A S E A 1 157 A S E A Y K
K V C 1 169 A P H E V G W K Y 1 177 Y Q A V T A T L E 1 201 Q L M R
L Q K Q A 1 213 M K K K I D K Y T 1 217 I D K Y T E S P G 1 220 Y T
E S P G G G S 1 221 T E S P G G G S P 1 244 A T R A T R I G H 1 267
P P A L S A R A P 1 270 L S A R A P V P A 1 275 P V P A A S P A A 1
280 S P A A W L P L R 1 282 A A W L P L R T P 1 284 W L P L R T P W
T 1 286 P L R T P W T R P 1 290 P W T R P S S C P 1 291 W T R P S S
C P T 1 295 S S C P T S S S T 1 304 Y D S L S P Y G P 1 307 L S P Y
G P R N P 1 310 Y G P R N P L P N 1 316 L P N P R H S P S 1 317 P N
P R H S P S G 1 323 P S G G G G L K K 1 329 L K K P A R H C Q 1 332
P A R H C Q G Q K 1 337 Q G Q K H N V L A 1 339 Q K H N V L A R G 1
341 H N V L A R G K P 1 344 L A R G K P Q R K 1 355 S E N N S W Y V
E 1 360 W Y V E N G R P A 1 361 Y V E N G R P A D 1 363 E N G R P A
D L A 1 369 D L A G S G Y C G 1 370 L A G S G Y C G A 1 379 L W K A
I E S L E 1 380 W K A I E S L E E 1 383 I E S L E E G L G 1 387 E E
G L G G K Q K 1
[0833]
40TABLE XXXIII SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:
HLA Peptide Scoring Results B*4402 9-mers SYFPEITHI 42 V E A E Q A
K V F 24 146 E D D T V V V A L 18 186 A V I A S F D Q L 18 153 A L
D L Q G V V F 17 162 P Y F P R L G R Y 17 34 A E N G P H L L V 16
69 A F G S G I H K I 16 159 V V F P Y F P R L 16 230 N T V P G V R
N Y 16 284 A Q I A K V G Q I 16 1 M K S L L L L V L 15 62 K F Y R D
P T A F 15 121 D A S L V I T D L 15 145 L E D D T V V V A 15 255 S
N F N G R F Y Y 15 264 L I H P T K L T Y 15 288 K V G Q I F A A W
15 329 E A A V R F V G F 15 2 K S L L L L V L I 14 10 I S I C W A D
H L 14 33 Q A E N G P H L L 14 44 A E Q A K V F S H 14 51 S H R G G
N V T L 14 56 N V T L P C K F Y 14 73 G I H K I R I K W 14 90 K E V
D V F V S M 14 97 S M G Y H K K T Y 14 180 A C L D Q D A V I 14 183
D Q D A V I A S F 14 190 S F D Q L Y D A W 14 209 W L S D G S V Q Y
14 256 N F N G R F Y Y L 14 278 A C L N D G A Q I 14 291 Q I F A A
W K I L 14 293 F A A W K I L G Y 14 336 G F P D K K H K L 14 337 F
P D K K H K L Y 14 345 Y G V Y C F R A Y 14 6 L L V L I S I C W 13
22 Y T L D H D R A I 13 55 G N V T L P C K F 13 87 D Y L K E V D V
F 13 118 S D S D A S L V I 13 123 S L V I T D L T L 13 126 I T D L
T L E D Y 13 131 L E D Y G R Y K C 13 137 Y K C E V I E G L 13 243
K D K S R Y D V F 13 249 D V F C F T S N F 13 262 Y Y L I H P T K L
13 290 G Q I F A A W K I 13 326 S P T E A A V R F 13 4 L L L L V L
I S I 12 16 D H L S D N Y T L 12 24 L D H D R A I H I 12 76 K I R I
K W T K L 12 80 K W T K L T S D Y 12 105 Y G G Y Q G R V F 12 106 G
G Y Q G R V F L 12 116 G G S D S D A S L 12 142 I E G L E D D T V
12 148 D T V V V A L D L 12 155 D L Q G V V F P Y 12 164 F P R L G
R Y N L 12 166 R L G R Y N L N F 12 175 H E A Q Q A C L D 12 194 L
Y D A W R G G L 12 196 D A W R G G L D W 12 202 L D W C N A G W L
12 233 P G V R N Y G F W 12 245 K S R Y D V F C F 12 253 F T S N F
N G R F 12 254 T S N F N G R F Y 12 273 D E A V Q A C L N 12 300 G
Y D R C D A G W 12 308 W L A D G S V R Y 12 310 A D G S V R Y P I
12 328 T E A A V R F V G 12 340 K K H K L Y G V Y 12 342 H K L Y G
V Y C F 12 14 W A D H L S D N Y 11 32 I Q A E N G P H L 11 81 W T K
L T S D Y L 11 129 L T L E D Y G R Y 11 139 C E V I E G L E D 11
156 L Q G V V F P Y F 11 187 V I A S F D Q L Y 11 201 G L D W C N A
G W 11 223 R E P C G G Q N T 11 232 V P G V R N Y G F 11 240 F W D
K D K S R Y 11 301 Y D R C D A G W L 11 92 V D V F V S M G Y 10 100
Y H K K T Y G G Y 10 174 F H E A Q Q A C L 10 257 F N G R F Y Y L I
10 272 Y D E A V Q A C L 10 285 Q I A K V G Q I F 10 71 G S G I H K
I R I 9 134 Y G R Y K C E V I 9 211 S D G S V Q Y P I 9 287 A K V G
Q I F A A 9 35 E N G P H L L V E 8 66 D P T A F G S G I 8 72 S G I
H K I R I K 8 77 I R I K W T K L T 7 122 A S L V I T D L T 7 189 A
S F D Q L Y D A 7 215 V Q Y P I T K P R 7 263 Y L I H P T K L T 7
335 V G F P D K K H K 7 8 V L I S I C W A D 6 25 D H D R A I H I Q
6 74 I H K I R I K W T 6 75 H K I R I K W T K 6 124 L V I T D L T L
E 6 132 E D Y G R Y K C E 6 140 E V I E G L E D D 6 217 Y P I T K P
R E P 6 316 Y P I S R P R R R 6 318 I S R P R R R C S 6 324 R C S P
T E A A V 6 3 S L L L L V L I S 5 15 A D H L S D N Y T 5 27 D R A I
H I Q A E 5 64 Y R D P T A F G S 5 70 F G S G I H K I R 5 84 L T S
D Y L K E V 5 96 V S M G Y H K K T 5 165 P R L G R Y N L N 5 177 A
Q Q A C L D Q D 5 182 L D Q D A V I A S 5 197 A W R G G L D W C 5
200 G G L D W C N A G 5 214 S V Q Y P I T K P 5 224 E P C G G Q N T
V 5 275 A V Q A C L N D G 5 280 L N D G A Q I A K 5 281 N D G A Q I
A K V 5 282 D G A Q I A K V G 5 294 A A W K I L G Y D 5 314 V R Y P
I S R P R 5 319 S R P R R R C S P 5 330 A A V R F V G F P 5 5 L L L
V L I S I C 4 7 L V L I S I C W A 4 17 H L S D N Y T L D 4 18 L S D
N Y T L D H 4 28 R A I H I Q A E N 4 29 A I H I Q A E N G 4 30 I H
I Q A E N G P 4 36 N G P H L L V E A 4 37 G P H L L V E A E 4 47 A
K V F S H R G G 4 48 K V F S H R G G N 4 52 H R G G N V T L P 4 57
V T L P C K F Y R 4 61 C K F Y R D P T A 4 68 T A F G S G I H K 4
91 E V D V F V S M G 4 107 G Y Q G R V F L K 4 108 Y Q G R V F L K
G 4 120 S D A S L V I T D 4 143 E G L E D D T V V 4 144 G L E D D T
V V V 4 160 V F P Y F P R L G 4 169 R Y N L N F H E A 4 170 Y N L N
F H E A Q 4 172 L N F H E A Q Q A 4 207 A G W L S D G S V 4 219 I T
K P R E P C G 4 222 P R E P C G G Q N 4 231 T V P G V R N Y G 4 259
G R F Y Y L I H P 4 260 R F Y Y L I H P T 4 268 T K L T Y D E A V 4
270 L T Y D E A V Q A 4 271 T Y D E A V Q A C 4 277 Q A C L N D G A
Q 4 296 W K I L G Y D R C 4 297 K I L G Y D R C D 4 299 L G Y D R C
D A G 4 303 R C D A G W L A D 4 306 A G W L A D G S V 4 309 L A D G
S V R Y P 4 313 S V R Y P I S R P 4 317 P I S R P R R R C 4 325 C S
P T E A A V R 4 11 S I C W A D H L S 3 26 H D R A I H I Q A 3 39 H
L L V E A E Q A 3 43 E A E Q A K V F S 3 45 E Q A K V F S H R 3 50
F S H R G G N V T 3 53 R G G N V T L P C 3 65 R D P T A F G S G 3
82 T K L T S D Y L K 3 83 K L T S D Y L K E 3 86 S D Y L K E V D V
3 95 F V S M G Y H K K 3 109 Q G R V F L K G G 3 111 R V F L K G G
S D 3 115 K G G S D S D A S 3 117 G S D S D A S L V 3 119 D S D A S
L V I T 3 125 V I T D L T L E D 3 138 K C E V I E G L E 3 152 V A L
D L Q G V V 3 154 L D L Q G V V F P 3 163 Y F P R L G R Y N 3 167 L
G R Y N L N F H 3 173 N F H E A Q Q A C 3 176 E A Q Q A C L D Q 3
179 Q A C L D Q D A V 3 181 C L D Q D A V I A 3 210 L S D G S V Q Y
P 3 213 G S V Q Y P I T K 3 220 T K P R E P C G G 3 226 C G G Q N T
V P G 3 228 G Q N T V P G V R 3 237 N Y G F W D K D K 3 238 Y G F W
D K D K S 3 239 G F W D K D K S R 3 244 D K S R Y D V F C 3 246 S R
Y D V F C F T 3 251 F C F T S N F N G 3 252 C F T S N F N G R 3 261
F Y Y L I H P T K 3 265 I H P T K L T Y D 3 274 E A V Q A C L N D 3
295 A W K I L G Y D R 3 312 G S V R Y P I S R 3 323 R R C S P T E A
A 3 331 A V R F V G F P D 3 332 V R F V G F P D K 3 333 R F V G F P
D K K 3 334 F V G F P D K K H 3 341 K H K L Y G V Y C 3 13 C W A D
H L S D N 2 19 S D N Y T L D H D 2 20 D N Y T L D H D R 2 21 N Y T
L D H D R A 2 23 T L D H D R A I H 2 38 P H L L V E A E Q 2 40 L L
V E A E Q A K 2 49 V F S H R G G N V 2 58 T L P C K F Y R D 2 63 F
Y R D P T A F G 2 78 R I K W T K L T S 2 79 I K W T K L T S D 2 85
T S D Y L K E V D 2 89 L K E V D V F V S 2 93 D V F V S M G Y H 2
102 K K T Y G G Y Q G 2 103 K T Y G G Y Q G R 2 127 T D L T L E D Y
G 2 130 T L E D Y G R Y K 2 136 R Y K C E V I E G 2 147 D D T V V V
A L D 2 149 T V V V A L D L Q 2 150 V V V A L D L Q G 2 151 V V A L
D L Q G V 2 161 F P Y F P R L G R 2 171 N L N F H E A Q Q 2 184 Q D
A V I A S F D 2 188 I A S F D Q L Y D 2 192 D Q L Y D A W R G 2 193
Q L Y D A W R G G 2 195 Y D A W R G G L D 2 203 D W C N A G W L S 2
205 C N A G W L S D G 2 208 G W L S D G S V Q 2 225 P C G G Q N T V
P 2 227 G G Q N T V P G V 2 236 R N Y G F W D K D 2 241 W D K D K S
R Y D 2 242 D K D K S R Y D V 2 247 R Y D V F C F T S 2 258 N G R F
Y Y L I H 2 269 K L T Y D E A V Q 2 279 C L N D G A Q I A 2 292 I F
A A W K I L G 2 302 D R C D A G W L A 2 304 C D A G W L A D G 2 307
G W L A D G S V R 2 311 D G S V R Y P I S 2 315 R Y P I S R P R R 2
320 R P R R R C S P T 2 321 P R R R C S P T E 2 327 P T E A A V R F
V 2 343 K L Y G V Y C F R 2 9 L I S I C W A D H 1 12 I C W A D H L
S D 1 41 L V E A E Q A K V 1 46 Q A K V F S H R G 1 54 G G N V T L
P C K 1 59 L P C K F Y R D P 1 60 P C K F Y R D P T 1 88 Y L K E V
D V F V 1 99 G Y H K K T Y G G 1 101 H K K T Y G G Y Q 1 104 T Y G
G Y Q G R V 1 112 V F L K G G S D S 1 113 F L K G G S D S D 1 114 L
K G G S D S D A 1 128 D L T L E D Y G R 1 133 D Y G R Y K C E V 1
135 G R Y K C E V I E 1 141 V I E G L E D D T 1 157 Q G V V F P Y F
P 1 168 G R Y N L N F H E 1 191 F D Q L Y D A W R 1 198 W R G G L D
W C N 1 199 R G G L D W C N A 1 204 W C N A G W L S D 1 206 N A G W
L S D G S 1 212 D G S V Q Y P I T 1 216 Q Y P I T K P R E 1 218 P I
T K P R E P C 1 221 K P R E P C G G Q 1 229 Q N T V P G V R N 1 234
G V R N Y G F W D 1 235 V R N Y G F W D K 1 248 Y D V F C F T S N 1
250 V F C F T S N F N 1 266 H P T K L T Y D E 1 267 P T K L T Y D E
A 1 283 G A Q I A K V G Q 1 286 I A K V G Q I F A 1 289 V G Q I F A
A W K 1 298 I L G Y D R C D A 1 305 D A G W L A D G S 1 322 R R R C
S P T E A 1 338 P D K K H K L Y G 1 339 D K K H K L Y G V 1 346 G V
Y C F R A Y N 1 151P3D4 v.2: HLA Peptide Scoring Results B*4402
9-mers SYFPEITHI 209 A E K N M K K K I 25 362 V E N G R P A D L 23
158 S E A Y K K V C L 22 192 A E I H Y R K N K 19 283 A W L P L R T
P W 18 99 E G I N I S G S F 17 185 E E K R K E K A E 17 371 A G S G
Y C G A L 17 51 A K D F G H V Q F 16 80 E K Q R K D K V L 16 123 N
T N P S R R P Y 16 226 G G S P R G L G F 16 378 A L W K A I E S L
16 387 E E G L G G K Q K 16 66 A Y S N D G E H W 15 104 S G S F C R
N K L 15 106 S F C R N K L K Y 15 125 N P S R R P Y H F 15 133 F Q
V P S R I F W 15 167 S G A P H E V G W 15 189 K E K A E I H Y R 15
212 N M K K K I D K Y 15 234 F I F K T I A P L 15 262 S S A H R P P
A L 15 279 A S P A A W L P L 15 400 K A E N G P H L L 15 1 M L E H
T T K T F 14 3 E H T T K T F P L 14 6 T K T F P L R A L 14 30 K Q D
K K V D L L 14 98 C E G I N I S G S 14 107 F C R N K L K Y L 14 109
R N K L K Y L A F 14 169 A P H E V G W K Y 14 194 I H Y R K N K Q L
14 221 T E S P G G G S P 14 296 S C P T S S S T Y 14 308 S P Y G P
R N P L 14 8 T F P L R A L H I 13 18 V E S I R D H S G 13 46 I I T
Q G A K D F 13 57 V Q F V G S Y K L 13 59 F V G S Y K L A Y 13 81 K
Q R K D K V L L 13 110 N K L K Y L A F L 13 176 K Y Q A V T A T L
13 224 P G G G S P R G L 13 231 G L G F I F K T I 13 276 V P A A S
P A A W 13 302 S T Y D S L S P Y 13 355 S E N N S W Y V E 13 382 A
I E S L E E G L 13 383 I E S L E E G L G 13 13 A L H I V V E S I 12
29 M K Q D K K V D L 12 69 N D G E H W T V Y 12 71 G E H W T V Y Q
D 12 79 D E K Q R K D K V 12 153 P Q G H A S E A Y 12 171 H E V G W
K Y Q A 12 184 L E E K R K E K A 12 228 S P R G L G F I F 12 336 C
Q G Q K H N V L 12 352 K P K S E N N S W 12 353 P K S E N N S W Y
12 367 P A D L A G S G Y 12 375 Y C G A L W K A I 12 386 L E E G L
G G K Q 12 397 K E R K A E N G P 12 2 L E H T T K T F P 11 38 L V P
T K V T G I 11 55 G H V Q F V G S Y 11 93 A V V V S C E G I 11 131
Y H F Q V P S R I 11 132 H F Q V P S R I F 11 188 R K E K A E I H Y
11 197 R K N K Q L M R L 11 227 G S P R G L G F I 11 242 L A A T R
A T R I 11 277 P A A S P A A W L 11 299 T S S S T Y D S L 11 321 H
S P S G G G G L 11 372 G S G Y C G A L W 11 399 R K A E N G P H L
11 95 V V S C E G I N I 10 143 Q E K A D G G S C 10 186 E K R K E K
A E I 10 39 V P T K V T G I I 9 272 A R A P V P A A S 9 278 A A S P
A A W L P 9 7 K T F P L R A L H 8 86 K V L L G R K A V 8 240 A P L
A A T R A T 8 264 A H R P P A L S A 8 314 N P L P N P R H S 8 42 K
V T G I I T Q G 7 150 S C C P Q G H A S 7 233 G F I F K T I A P 7
237 K T I A P L A A T 7 265 H R P P A L S A R 7 269 A L S A R A P V
P 7 274 A P V P A A S P A 7 282 A A W L P L R T P 7 364 N G R P A D
L A G 7 11 L R A L H I V V E 6 19 E S I R D H S G Q 6 41 T K V T G
I I T Q 6 105 G S F C R N K L K 6 157 A S E A Y K K V C 6 182 A T L
E E K R K E 6 230 R G L G F I F K T 6 243 A A T R A T R I G 6 324 S
G G G G L K K P 6 346 R G K P Q R K P K 6 394 Q K D K E R K A E 6
34 K V D L L V P T K 5 36 D L L V P T K V T 5 37 L L V P T K V T G
5 44 T G I I T Q G A K 5 45 G I I T Q G A K D 5 52 K D F G H V Q F
V 5 113 K Y L A F L H K R 5 116 A F L H K R M N T 5 127 S R R P Y H
F Q V 5 134 Q V P S R I F W R 5 137 S R I F W R Q E K 5 139 I F W R
Q E K A D 5 193 E I H Y R K N K Q 5 199 N K Q L M R L Q K 5 200 K Q
L M R L Q K Q 5 201 Q L M R L Q K Q A 5 215 K K I D K Y T E S 5 238
T I A P L A A T R 5 244 A T R A T R I G H 5 245 T R A T R I G H P 5
248 T R I G H P G G R 5 250 I G H P G G R T P 5 253 P G G R T P R A
G 5 255 G R T P R A G S S 5 260 A G S S A H R P P 5 267 P P A L S A
R A P 5 287 L R T P W T R P S 5 306 S L S P Y G P R N 5 309 P Y G P
R N P L P 5 310 Y G P R N P L P N 5 312 P R N P L P N P R 5 329 L K
K P A R H C Q 5 338 G Q K H N V L A R 5 342 N V L A R G K P Q 5 345
A R G K P Q R K P 5 348 K P Q R K P K S E 5 363 E N G R P A D L A 5
381 K A I E S L E E G 5 388 E G L G G K Q K D 5 9 F P L R A L H I V
4 12 R A L H I V V E S 4 16 I V V E S I R D H 4 27 Q K M K Q D K K
V 4 28 K M K Q D K K V D 4 33 K K V D L L V P T 4 35 V D L L V P T
K V 4 58 Q F V G S Y K L A 4 68 S N D G E H W T V 4 82 Q R K D K V
L L G 4 87 V L L G R K A V V 4 88 L L G R K A V V V 4 96 V S C E G
I N I S 4 97 S C E G I N I S G 4 102 N I S G S F C R N 4 115 L A F
L H K R M N 4 135 V P S R I F W R Q 4 138 R I F W R Q E K A 4 146 A
D G G S C C P Q 4 156 H A S E A Y K K V 4 159 E A Y K K V C L S 4
160 A Y K K V C L S G 4 165 C L S G A P H E V 4 172 E V G W K Y Q A
V 4 179 A V T A T L E E K 4 208 Q A E K N M K K K 4 210 E K N M K K
K I D 4 222 E S P G G G S P R 4 235 I F K T I A P L A 4 236 F K T I
A P L A A 4 263 S A H R P P A L S 4 271 S A R A P V P A A 4 284 W L
P L R T P W T 4 285 L P L R T P W T R 4 295 S S C P T S S S T 4 300
S S S T Y D S L S 4 315 P L P N P R H S P 4 316 L P N P R H S P S 4
320 R H S P S G G G G 4 322 S P S G G G G L K 4 330 K K P A R H C Q
G 4 333 A R H C Q G Q K H 4 361 Y V E N G R P A D 4 368 A D L A G S
G Y C 4 384 E S L E E G L G G 4 393 K Q K D K E R K A 4 5 T T K T F
P L R A 3 14 L H I V V E S I R 3 20 S I R D H S G Q K 3 23 D H S G
Q K M K Q 3 24 H S G Q K M K Q D 3 32 D K K V D L L V P 3 50 G A K
D F G H V Q 3 72 E H W T V Y Q D E 3 75 T V Y Q D E K Q R 3 77 Y Q
D E K Q R K D 3 78 Q D E K Q R K D K 3 83 R K D K V L L G R 3 85 D
K V L L G R K A 3 89 L G R K A V V V S 3 101 I N I S G S F C R 3
111 K L K Y L A F L H 3 112 L K Y L A F L H K 3 117 F L H K R M N T
N 3 119 H K R M N T N P S 3 120 K R M N T N P S R 3 121 R M N T N P
S R R 3 124 T N P S R R P Y H 3 128 R R P Y H F Q V P 3 144 E K A D
G G S C C 3 145 K A D G G S C C P 3 162 K K V C L S G A P 3 174 G W
K Y Q A V T A 3 175 W K Y Q A V T A T 3 178 Q A V T A T L E E 3 181
T A T L E E K R K 3 183 T L E E K R K E K 3 190 E K A E I H Y R K 3
191 K A E I H Y R K N 3 198 K N K Q L M R L Q 3 202 L M R L Q K Q A
E 3 211 K N M K K K I D K 3 213 M K K K I D K Y T 3 216 K I D K Y T
E S P 3 229 P R G L G F I F K 3 239 I A P L A A T R A 3 243 R A T R
I G H P G 3 247 A T R I G H P G G 3 251 G H P G G R T P R 3 252 H P
G G R T P R A 3 270 L S A R A P V P A 3 275 P V P A A S P A A 3 280
S P A A W L P L R 3 289 T P W T R P S S C 3 291 W T R P S S C P T 3
304 Y D S L S P Y G P 3 307 L S P Y G P R N
P 3 323 P S G G G G L K K 3 325 G G G G L K K P A 3 326 G G G L K K
P A R 3 340 K H N V L A R G K 3 341 H N V L A R G K P 3 347 G K P Q
R K P K S 3 350 Q R K P K S E N N 3 354 K S E N N S W Y V 3 356 E N
N S W Y V E N 3 357 N N S W Y V E N G 3 373 S G Y C G A L W K 3 374
G Y C G A L W K A 3 377 G A L W K A I E S 3 389 G L G G K Q K D K 3
4 H T T K T F P L R 2 10 P L R A L H I V V 2 17 V V E S I R D H S 2
21 I R D H S G Q K M 2 22 R D H S G Q K M K 2 31 Q D K K V D L L V
2 43 V T G I I T Q G A 2 54 F G H V Q F V G S 2 60 V G S Y K L A Y
S 2 62 S Y K L A Y S N D 2 63 Y K L A Y S N D G 2 67 Y S N D G E H
W T 2 70 D G E H W T V Y Q 2 84 K D K V L L G R K 2 90 G R K A V V
V S C 2 114 Y L A F L H K R M 2 122 M N T N P S R R P 2 126 P S R R
P Y H F Q 2 136 P S R I F W R Q E 2 148 G G S C C P Q G H 2 152 C P
Q G H A S E A 2 155 G H A S E A Y K K 2 163 K V C L S G A P H 2 164
V C L S G A P H E 2 168 G A P H E V G W K 2 170 P H E V G W K Y Q 2
177 Y Q A V T A T L E 2 180 V T A T L E E K R 2 187 K R K E K A E I
H 2 195 H Y R K N K Q L M 2 196 Y R K N K Q L M R 2 204 R L Q K Q A
E K N 2 205 L Q K Q A E K N M 2 207 K Q A E K N M K K 2 214 K K K I
D K Y T E 2 219 K Y T E S P G G G 2 223 S P G G G S P R G 2 225 G G
G S P R G L G 2 232 L G F I F K T I A 2 241 P L A A T R A T R 2 254
G G R T P R A G S 2 256 R T P R A G S S A 2 257 T P R A G S S A H 2
259 R A G S S A H R P 2 261 G S S A H R P P A 2 268 P A L S A R A P
V 2 273 R A P V P A A S P 2 281 P A A W L P L R T 2 288 R T P W T R
P S S 2 292 T R P S S C P T S 2 293 R P S S C P T S S 2 294 P S S C
P T S S S 2 298 P T S S S T Y D S 2 301 S S T Y D S L S P 2 311 G P
R N P L P N P 2 313 R N P L P N P R H 2 317 P N P R H S P S G 2 318
N P R H S P S G G 2 327 G G L K K P A R H 2 328 G L K K P A R H C 2
331 K P A R H C Q G Q 2 334 R H C Q G Q K H N 2 335 H C Q G Q K H N
V 2 337 Q G Q K H N V L A 2 339 Q K H N V L A R G 2 343 V L A R G K
P Q R 2 344 L A R G K P Q R K 2 351 R K P K S E N N S 2 358 N S W Y
V E N G R 2 360 W Y V E N G R P A 2 365 G R P A D L A G S 2 366 R P
A D L A G S G 2 379 L W K A I E S L E 2 385 S L E E G L G G K 2 391
G G K Q K D K E R 2 395 K D K E R K A E N 2 396 D K E R K A E N G 2
398 E R K A E N G P H 2 15 H I V V E S I R D 1 25 S G Q K M K Q D K
1 26 G Q K M K Q D K K 1 40 P T K V T G I I T 1 47 I T Q G A K D F
G 1 49 Q G A K D F G H V 1 53 D F G H V Q F V G 1 61 G S Y K L A Y
S N 1 64 K L A Y S N D G E 1 65 L A Y S N D G E H 1 74 W T V Y Q D
E K Q 1 76 V Y Q D E K Q R K 1 91 R K A V V V S C E 1 92 K A V V V
S C E G 1 103 I S G S F C R N K 1 108 C R N K L K Y L A 1 118 L H K
R M N T N P 1 129 R P Y H F Q V P S 1 130 P Y H F Q V P S R 1 141 W
R Q E K A D G G 1 147 D G G S C C P Q G 1 151 C C P Q G H A S E 1
161 Y K K V C L S G A 1 166 L S G A P H E V G 1 173 V G W K Y Q A V
T 1 203 M R L Q K Q A E K 1 206 Q K Q A E K N M K 1 218 D K Y T E S
P G G 1 258 P R A G S S A H R 1 266 R P P A L S A R A 1 286 P L R T
P W T R P 1 290 P W T R P S S C P 1 303 T Y D S L S P Y G 1 305 D S
L S P Y G P R 1 332 P A R H C Q G Q K 1 359 S W Y V E N G R P 1 369
D L A G S G Y C G 1 376 C G A L W K A I E 1 380 W K A I E S L E E 1
390 L G G K Q K D K E 1
[0834]
41TABLE XXXIV SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:
HLA Peptide Scoring Results B*5101 9-mers SYFPEITHI 66 D P T A F G
S G I 25 152 V A L D L Q G V V 25 121 D A S L V I T D L 24 134 Y G
R Y K C E V I 22 143 E G L E D D T V V 22 224 E P C G G Q N T V 22
4 L L L L V L I S I 18 179 Q A C L D Q D A V 18 33 Q A E N G P H L
L 17 106 G G Y Q G R V F L 17 164 F P R L G R Y N L 17 227 G G Q N
T V P G V 17 309 L A D G S V R Y P 17 22 Y T L D H D R A I 16 24 L
D H D R A I H I 16 68 T A F G S G I H K 16 161 F P Y F P R L G R 16
180 A C L D Q D A V I 16 196 D A W R G G L D W 16 207 A G W L S D G
S V 16 217 Y P I T K P R E P 16 16 D H L S D N Y T L 15 88 Y L K E
V D V F V 15 118 S D S D A S L V I 15 282 D G A Q I A K V G 15 305
D A G W L A D G S 15 306 A G W L A D G S V 15 316 Y P I S R P R R R
15 326 S P T E A A V R F 15 2 K S L L L L V L I 14 59 L P C K F Y R
D P 14 84 L T S D Y L K E V 14 86 S D Y L K E V D V 14 116 G G S D
S D A S L 14 148 D T V V V A L D L 14 185 D A V I A S F D Q 14 242
D K D K S R Y D V 14 262 Y Y L I H P T K L 14 284 A Q I A K V G Q I
14 293 F A A W K I L G Y 14 337 F P D K K H K L Y 14 339 D K K H K
L Y G V 14 41 L V E A E Q A K V 13 69 A F G S G I H K I 13 98 M G Y
H K K T Y G 13 133 D Y G R Y K C E V 13 137 Y K C E V I E G L 13
144 G L E D D T V V V 13 188 I A S F D Q L Y D 13 268 T K L T Y D E
A V 13 281 N D G A Q I A K V 13 286 I A K V G Q I F A 13 290 G Q I
F A A W K I 13 294 A A W K I L G Y D 13 299 L G Y D R C D A G 13 1
M K S L L L L V L 12 37 G P H L L V E A E 12 71 G S G I H K I R I
12 87 D Y L K E V D V F 12 104 T Y G G Y Q G R V 12 105 Y G G Y Q G
R V F 12 142 I E G L E D D T V 12 146 E D D T V V V A L 12 211 S D
G S V Q Y P I 12 221 K P R E P C G G Q 12 232 V P G V R N Y G F 12
278 A C L N D G A Q I 12 310 A D G S V R Y P I 12 327 P T E A A V R
F V 12 329 E A A V R F V G F 12 330 A A V R F V G F P 12 32 I Q A E
N G P H L 11 43 E A E Q A K V F S 11 46 Q A K V F S H R G 11 51 S H
R G G N V T L 11 159 V V F P Y F P R L 11 176 E A Q Q A C L D Q 11
206 N A G W L S D G S 11 238 Y G F W D K D K S 11 257 F N G R F Y Y
L I 11 266 H P T K L T Y D E 11 272 Y D E A V Q A C L 11 274 E A V
Q A C L N D 11 283 G A Q I A K V G Q 11 336 G F P D K K H K L 11 10
I S I C W A D H L 10 14 W A D H L S D N Y 10 28 R A I H I Q A E N
10 34 A E N G P H L L V 10 36 N G P H L L V E A 10 76 K I R I K W T
K L 10 123 S L V I T D L T L 10 145 L E D D T V V V A 10 151 V V A
L D L Q G V 10 167 L G R Y N L N F H 10 200 G G L D W C N A G 10
202 L D W C N A G W L 10 212 D G S V Q Y P I T 10 277 Q A C L N D G
A Q 10 311 D G S V R Y P I S 10 320 R P R R R C S P T 10 335 V G F
P D K K H K 10 345 Y G V Y C F R A Y 10 20 D N Y T L D H D R 9 49 V
F S H R G G N V 9 53 R G G N V T L P C 9 70 F G S G I H K I R 9 72
S G I H K I R I K 9 117 G S D S D A S L V 9 155 D L Q G V V F P Y 9
186 A V I A S F D Q L 9 194 L Y D A W R G G L 9 256 N F N G R F Y Y
L 9 258 N G R F Y Y L I H 9 270 L T Y D E A V Q A 9 291 Q I F A A W
K I L 9 301 Y D R C D A G W L 9 324 R C S P T E A A V 9 42 V E A E
Q A K V F 8 54 G G N V T L P C K 8 108 Y Q G R V F L K G 8 109 Q G
R V F L K G G 8 119 D S D A S L V I T 8 147 D D T V V V A L D 8 174
F H E A Q Q A C L 8 183 D Q D A V I A S F 8 192 D Q L Y D A W R G 8
246 S R Y D V F C F T 8 289 V G Q I F A A W K 8 79 I K W T K L T S
D 7 81 W T K L T S D Y L 7 89 L K E V D V F V S 7 129 L T L E D Y G
R Y 7 154 L D L Q G V V F P 7 157 Q G V V F P Y F P 7 226 C G G Q N
T V P G 7 228 G Q N T V P G V R 7 236 R N Y G F W D K D 7 261 F Y Y
L I H P T K 7 265 I H P T K L T Y D 7 328 T E A A V R F V G 7 343 K
L Y G V Y C F R 7 7 L V L I S I C W A 6 62 K F Y R D P T A F 6 93 D
V F V S M G Y H 6 96 V S M G Y H K K T 6 115 K G G S D S D A S 6
132 E D Y G R Y K C E 6 135 G R Y K C E V I E 6 168 G R Y N L N F H
E 6 182 L D Q D A V I A S 6 193 Q L Y D A W R G G 6 199 R G G L D W
C N A 6 210 L S D G S V Q Y P 6 215 V Q Y P I T K P R 6 225 P C G G
Q N T V P 6 231 T V P G V R N Y G 6 233 P G V R N Y G F W 6 244 D K
S R Y D V F C 6 264 L I H P T K L T Y 6 307 G W L A D G S V R 6 314
V R Y P I S R P R 6 325 C S P T E A A V R 6 3 S L L L L V L I S 5 5
L L L V L I S I C 5 12 I C W A D H L S D 5 25 D H D R A I H I Q 5
27 D R A I H I Q A E 5 35 E N G P H L L V E 5 45 E Q A K V F S H R
5 50 F S H R G G N V T 5 58 T L P C K F Y R D 5 82 T K L T S D Y L
K 5 90 K E V D V F V S M 5 103 K T Y G G Y Q G R 5 120 S D A S L V
I T D 5 124 L V I T D L T L E 5 156 L Q G V V F P Y F 5 208 G W L S
D G S V Q 5 213 G S V Q Y P I T K 5 249 D V F C F T S N F 5 251 F C
F T S N F N G 5 259 G R F Y Y L I H P 5 260 R F Y Y L I H P T 5 271
T Y D E A V Q A C 5 273 D E A V Q A C L N 5 297 K I L G Y D R C D 5
302 D R C D A G W L A 5 18 L S D N Y T L D H 4 38 P H L L V E A E Q
4 40 L L V E A E Q A K 4 44 A E Q A K V F S H 4 52 H R G G N V T L
P 4 55 G N V T L P C K F 4 64 Y R D P T A F G S 4 73 G I H K I R I
K W 4 74 I H K I R I K W T 4 77 I R I K W T K L T 4 78 R I K W T K
L T S 4 85 T S D Y L K E V D 4 100 Y H K K T Y G G Y 4 112 V F L K
G G S D S 4 114 L K G G S D S D A 4 126 I T D L T L E D Y 4 127 T D
L T L E D Y G 4 128 D L T L E D Y G R 4 130 T L E D Y G R Y K 4 131
L E D Y G R Y K C 4 153 A L D L Q G V V F 4 160 V F P Y F P R L G 4
163 Y F P R L G R Y N 4 165 P R L G R Y N L N 4 170 Y N L N F H E A
Q 4 172 L N F H E A Q Q A 4 203 D W C N A G W L S 4 214 S V Q Y P I
T K P 4 230 N T V P G V R N Y 4 239 G F W D K D K S R 4 248 Y D V F
C F T S N 4 280 L N D G A Q I A K 4 292 I F A A W K I L G 4 333 R F
V G F P D K K 4 334 F V G F P D K K H 4 340 K K H K L Y G V Y 4 342
H K L Y G V Y C F 4 344 L Y G V Y C F R A 4 346 G V Y C F R A Y N 4
6 L L V L I S I C W 3 19 S D N Y T L D H D 3 30 I H I Q A E N G P 3
39 H L L V E A E Q A 3 57 V T L P C K F Y R 3 61 C K F Y R D P T A
3 65 R D P T A F G S G 3 83 K L T S D Y L K E 3 92 V D V F V S M G
Y 3 94 V F V S M G Y H K 3 95 F V S M G Y H K K 3 97 S M G Y H K K
T Y 3 107 G Y Q G R V F L K 3 125 V I T D L T L E D 3 136 R Y K C E
V I E G 3 140 E V I E G L E D D 3 150 V V V A L D L Q G 3 162 P Y F
P R L G R Y 3 166 R L G R Y N L N F 3 173 N F H E A Q Q A C 3 189 A
S F D Q L Y D A 3 216 Q Y P I T K P R E 3 220 T K P R E P C G G 3
240 F W D K D K S R Y 3 241 W D K D K S R Y D 3 243 K D K S R Y D V
F 3 250 V F C F T S N F N 3 253 F T S N F N G R F 3 263 Y L I H P T
K L T 3 269 K L T Y D E A V Q 3 275 A V Q A C L N D G 3 285 Q I A K
V G Q I F 3 308 W L A D G S V R Y 3 312 G S V R Y P I S R 3 315 R Y
P I S R P R R 3 318 I S R P R R R C S 3 322 R R R C S P T E A 3 332
V R F V G F P D K 3 9 L I S I C W A D H 2 13 C W A D H L S D N 2 15
A D H L S D N Y T 2 17 H L S D N Y T L D 2 21 N Y T L D H D R A 2
26 H D R A I H I Q A 2 31 H I Q A E N G P H 2 47 A K V F S H R G G
2 56 N V T L P C K F Y 2 63 F Y R D P T A F G 2 75 H K I R I K W T
K 2 91 E V D V F V S M G 2 99 G Y H K K T Y G G 2 101 H K K T Y G G
Y Q 2 111 R V F L K G G S D 2 113 F L K G G S D S D 2 122 A S L V I
T D L T 2 141 V I E G L E D D T 2 149 T V V V A L D L Q 2 177 A Q Q
A C L D Q D 2 181 C L D Q D A V I A 2 191 F D Q L Y D A W R 2 195 Y
D A W R G G L D 2 197 A W R G G L D W C 2 204 W C N A G W L S D 2
205 C N A G W L S D G 2 209 W L S D G S V Q Y 2 219 I T K P R E P C
G 2 229 Q N T V P G V R N 2 235 V R N Y G F W D K 2 237 N Y G F W D
K D K 2 245 K S R Y D V F C F 2 247 R Y D V F C F T S 2 252 C F T S
N F N G R 2 254 T S N F N G R F Y 2 276 V Q A C L N D G A 2 279 C L
N D G A Q I A 2 287 A K V G Q I F A A 2 298 I L G Y D R C D A 2 303
R C D A G W L A D 2 304 C D A G W L A D G 2 313 S V R Y P I S R P 2
317 P I S R P R R R C 2 321 P R R R C S P T E 2 331 A V R F V G F P
D 2 338 P D K K H K L Y G 2 341 K H K L Y G V Y C 2 8 V L I S I C W
A D 1 23 T L D H D R A I H 1 29 A I H I Q A E N G 1 48 K V F S H R
G G N 1 60 P C K F Y R D P T 1 80 K W T K L T S D Y 1 139 C E V I E
G L E D 1 169 R Y N L N F H E A 1 171 N L N F H E A Q Q 1 175 H E A
Q Q A C L D 1 184 Q D A V I A S F D 1 187 V I A S F D Q L Y 1 198 W
R G G L D W C N 1 201 G L D W C N A G W 1 218 P I T K P R E P C 1
223 R E P C G G Q N T 1 234 G V R N Y G F W D 1 255 S N F N G R F Y
Y 1 267 P T K L T Y D E A 1 288 K V G Q I F A A W 1 296 W K I L G Y
D R C 1 319 S R P R R R C S P 1 151P3D4 v.2: HLA Peptide Scoring
Results B*5101 9-mers SYFPEITHI 242 L A A T R A T R I 26 39 V P T K
V T G I I 24 156 H A S E A Y K K V 23 9 F P L R A L H I V 22 308 S
P Y G P R N P L 22 268 P A L S A R A P V 20 38 L V P T K V T G I 18
159 E A Y K K V C L S 18 285 L P L R T P W T R 18 35 V D L L V P T
K V 17 49 Q G A K D F G H V 17 131 Y H F Q V P S R I 17 277 P A A S
P A A W L 17 400 K A E N G P H L L 17 65 L A Y S N D G E H 16 88 L
L G R K A V V V 16 169 A P H E V G W K Y 16 224 P G G G S P R G L
16 239 I A P L A A T R A 16 314 N P L P N P R H S 16 344 L A R G K
P Q R K 16 8 T F P L R A L H I 15 12 R A L H I V V E S 15 87 V L L
G R K A V V 15 89 L G R K A V V V S 15 104 S G S F C R N K L 15 129
R P Y H F Q V P S 15 194 I H Y R K N K Q L 15 282 A A W L P L R T P
15 377 G A L W K A I E S 15 13 A L H I V V E S I 14 50 G A K D F G
H V Q 14 79 D E K Q R K D K V 14 115 L A F L H K R M N 14 208 Q A E
K N M K K K 14 209 A E K N M K K K I 14 231 G L G F I F K T I 14
240 A P L A A T R A T 14 276 V P A A S P A A W 14 289 T P W T R P S
S C 14 371 A G S G Y C G A L 14 375 Y C G A L W K A I 14 381 K A I
E S L E E G 14 10 P L R A L H I V V 13 125 N P S R R P Y H F 13 135
V P S R I F W R Q 13 168 G A P H E V G W K 13 173 V G W K Y Q A V T
13 181 T A T L E E K R K 13 191 K A E I H Y R K N 13 259 R A G S S
A H R P 13 266 R P P A L S A R A 13 267 P P A L S A R A P 13 271 S
A R A P V P A A 13 281 P A A W L P L R T 13 318 N P R H S P S G G
13 348 K P Q R K P K S E 13 27 Q K M K Q D K K V 12 31 Q D K K V D
L L V 12 52 K D F G H V Q F V 12 92 K A V V V S C E G 12 95 V V S C
E G I N I 12 110 N K L K Y L A F L 12 152 C P Q G H A S E A 12 178
Q A V T A T L E E 12 223 S P G G G S P R G 12 227 G S P R G L G F I
12 230 R G L G F I F K T 12 252 H P G G R T P R A 12 257 T P R A G
S S A H 12 273 R A P V P A A S P 12 280 S P A A W L P L R 12 293 R
P S S C P T S S 12 297 C P T S S S T Y D 12 316 L P N P R H S P S
12 327 G G L K K P A R H 12 352 K P K S E N N S W 12 366 R P A D L
A G S G 12 370 L A G S G Y C G A 12 373 S G Y C G A L W K 12 68 S N
D G E H W T V 11 70 D G E H W T V Y Q 11 80 E K Q R K D K V L 11 86
K V L L G R K A V 11 93 A V V V S C E G I 11 145 K A D G G S C C P
11 176 K Y Q A V T A T L 11 186 E K R K E K A E I 11 228 S P R G L
G F I F 11 234 F I F K T I A P L 11 243 A A T R A T R I G 11 250 I
G H P G G R T P 11 263 S A H R P P A L S 11 274 A P V P A A S P A
11 278 A A S P A A W L P 11 310 Y G P R N P L P N 11 311 G P R N P
L P N P 11 322 S P S G G G G L K 11 324 S G G G G L K K P 11 336 C
Q G Q K H N V L 11 388 E G L G G K Q K D 11 390 L G G K Q K D K E
11 29 M K Q D K K V D L 10 30 K Q D K K V D L L 10 36 D L L V P T K
V T 10 57 V Q F V G S Y K L 10 107 F C R N K L K Y L 10 147 D G G S
C C P Q G 10 165 C L S G A P H E V 10 232 L G F I F K T I A 10 246
R A T R I G H P G 10 331 K P A R H C Q G Q 10 332 P A R H C Q G Q K
10 367 P A D L A G S G Y 10 6 T K T F P L R A L 9 32 D K K V D L L
V P 9 53 D F G H V Q F V G 9 54 F G H V Q F V G S 9 60 V G S Y K L
A Y S 9 112 L K Y L A F L H K 9 127 S R R P Y H F Q V 9 172 E V G W
K Y Q A V 9 197 R K N K Q L M R L 9 218 D K Y T E S P G G 9 253 P G
G R T P R A G 9 279 A S P A A W L P L 9 335 H C Q G Q K H N V 9 337
Q G Q K H N V L A 9 362 V E N G R P A D L 9 378 A L W K A I E S L 9
399 R K A E N G P H L 9 3 E H T T K T F P L 8 25 S G Q K M K Q D K
8 44 T G I I T Q G A K 8 77 Y Q D E K Q R K D 8 81 K Q R K D K V L
L 8 154 Q G H A S E A Y K 8 158 S E A Y K K V C L 8 299 T S S S T Y
D S L 8 325 G G G G L K K P A 8 354 K S E N N S W Y V 8 364 N G R P
A D L A G 8 391 G G K Q K D K E R 8 11 L R A L H I V V E 7 16 I V V
E S I R D H 7 23 D H S G Q K M K Q 7 63 Y K L A Y S N D G 7 69 N D
G E H W T V Y 7 85 D K V L L G R K A 7 148 G G S C C P Q G H 7 167
S G A P H E V G W 7 175 W K Y Q A V T A T 7 182 A T L E E K R K E 7
226 G G S P R G L G F 7 254 G G R T P R A G S 7 260 A G S S A H R P
P 7 262 S S A H R P P A L 7 302 S T Y D S L S P Y 7 321 H S P S G G
G G L 7 326 G G G L K K P A R 7 346 R G K P Q R K P K 7 37 L L V P
T K V T G 6 41 T K V T G I I T Q 6 61 G S Y K L A Y S N 6 75 T V Y
Q D E K Q R 6 90 G R K A V V V S C 6 99 E G I N I S G S F 6 113 K Y
L A F L H K R 6 157 A S E A Y K K V C 6 166 L S G A P H E V G 6 207
K Q A E K N M K K 6 212 N M K K K I D K Y 6 225 G G G S P R G L G 6
305 D S L S P Y G P R 6 359 S W Y V E N G R P 6 369 D L A G S G Y C
G 6 376 C G A L W K A I E 6 382 A I E S L E E G L 6 396 D K E R K A
E N G 6 1 M L E H T T K T F 5 2 L E H T T K T F P 5 5 T T K T F P L
R A 5 21 I R D H S G Q K M 5 82 Q R K D K V L L G 5 83 R K D K V L
L G R 5 96 V S C E G I N I S 5 102 N I S G S F C R N 5 117 F L H K
R M N T N 5 118 L H K R M N T N P 5 128 R R P Y H F Q V P 5 164 V C
L S G A P H E 5 177 Y Q A V T A T L E 5 183 T L E E K R K E K 5 184
L E E K R K E K A 5 200 K Q L M R L Q K Q 5 269 A L S A R A P V P 5
292 T R P S S C P T S 5 296 S C P T S S S T Y 5 307 L S P Y G P R N
P 5 342 N V L A R G K P Q 5 358 N S W Y V E N G R 5 384 E S L E E G
L G G 5 386 L E E G L G G K Q 5 393 K Q K D K E R K A 5 14 L H I V
V E S I R 4 28 K M K Q D K K V D 4 34 K V D L L V P T K 4 46 I I T
Q G A K D F 4 72 E H W T V Y Q D E 4 91 R K A V V V S C E 4 114 Y L
A F L H K R M 4 139 I F W R Q E K A D 4 141 W R Q E K A D G G 4 160
A Y K K V C L S G 4 174 G W K Y Q A V T A 4 180 V T A T L E E K R 4
187 K R K E K A E I H 4 196 Y R K N K Q L M R 4 203 M R L Q K Q A E
K 4 204 R L Q K Q A E K N 4 219 K Y T E S P G G G 4 235 I F K T I A
P L A 4 238 T I A P L A A T R 4 241 P L A A T R A T R 4 245 T R A T
R I G H P 4 270 L S A R A P V P A 4 304 Y D S L S P Y G P 4 323 P S
G G G G L K K 4 328 G L K K P A R H C 4 339 Q K H N V L A R G 4 345
A R G K P Q R K P 4 351 R K P K S E N N S 4 355 S E N N S W Y V E 4
357 N N S W Y V E N G 4 374 G Y C G A L W K A 4 4 H T T K T F P L R
3 26 G Q K M K Q D K K 3 33 K K V D L L V P T 3 42 K V T G I I T Q
G 3 45 G I I T Q G A K D 3 47 I T Q G A K D F G 3 48 T Q G A K D F
G H 3 58 Q F V G S Y K L A 3 59 F V G S Y K L A Y 3 67 Y S N D G E
H W T 3 71 G E H W T V Y Q D 3 76 V Y Q D E K Q R K 3 97 S C E G I
N I S G 3 103 I S G S F C R N K 3 105 G S F C R N K L K 3 106 S F C
R N K L K Y 3 116 A F L H K R M N T 3 121 R M N T N P
S R R 3 122 M N T N P S R R P 3 123 N T N P S R R P Y 3 133 F Q V P
S R I F W 3 138 R I F W R Q E K A 3 155 G H A S E A Y K K 3 161 Y K
K V C L S G A 3 179 A V T A T L E E K 3 188 R K E K A E I H Y 3 190
E K A E I H Y R K 3 193 E I H Y R K N K Q 3 199 N K Q L M R L Q K 3
205 L Q K Q A E K N M 3 211 K N M K K K I D K 3 213 M K K K I D K Y
T 3 215 K K I D K Y T E S 3 217 I D K Y T E S P G 3 236 F K T I A P
L A A 3 244 A T R A T R I G H 3 248 T R I G H P G G R 3 251 G H P G
G R T P R 3 258 P R A G S S A H R 3 272 A R A P V P A A S 3 283 A W
L P L R T P W 3 286 P L R T P W T R P 3 287 L R T P W T R P S 3 313
R N P L P N P R H 3 338 G Q K H N V L A R 3 347 G K P Q R K P K S 3
353 P K S E N N S W Y 3 360 W Y V E N G R P A 3 365 G R P A D L A G
S 3 368 A D L A G S G Y C 3 379 L W K A I E S L E 3 385 S L E E G L
G G K 3 389 G L G G K Q K D K 3 15 H I V V E S I R D 2 17 V V E S I
R D H S 2 24 H S G Q K M K Q D 2 40 P T K V T G I I T 2 55 G H V Q
F V G S Y 2 56 H V Q F V G S Y K 2 64 K L A Y S N D G E 2 74 W T V
Y Q D E K Q 2 78 Q D E K Q R K D K 2 84 K D K V L L G R K 2 101 I N
I S G S F C R 2 109 R N K L K Y L A F 2 120 K R M N T N P S R 2 124
T N P S R R P Y H 2 130 P Y H F Q V P S R 2 134 Q V P S R I F W R 2
146 A D G G S C C P Q 2 185 E E K R K E K A E 2 189 K E K A E I H Y
R 2 192 A E I H Y R K N K 2 202 L M R L Q K Q A E 2 206 Q K Q A E K
N M K 2 210 E K N M K K K I D 2 214 K K K I D K Y T E 2 216 K I D K
Y T E S P 2 220 Y T E S P G G G S 2 222 E S P G G G S P R 2 229 P R
G L G F I F K 2 233 G F I F K T I A P 2 237 K T I A P L A A T 2 264
A H R P P A L S A 2 265 H R P P A L S A R 2 275 P V P A A S P A A 2
288 R T P W T R P S S 2 300 S S S T Y D S L S 2 306 S L S P Y G P R
N 2 312 P R N P L P N P R 2 329 L K K P A R H C Q 2 330 K K P A R H
C Q G 2 333 A R H C Q G Q K H 2 334 R H C Q G Q K H N 2 340 K H N V
L A R G K 2 341 H N V L A R G K P 2 361 Y V E N G R P A D 2 383 I E
S L E E G L G 2 392 G K Q K D K E R K 2 394 Q K D K E R K A E 2 395
K D K E R K A E N 2 397 K E R K A E N G P 2 398 E R K A E N G P H 2
7 K T F P L R A L H 1 18 V E S I R D H S G 1 20 S I R D H S G Q K 1
22 R D H S G Q K M K 1 43 V T G I I T Q G A 1 51 A K D F G H V Q F
1 66 A Y S N D G E H W 1 73 H W T V Y Q D E K 1 94 V V V S C E G I
N 1 98 C E G I N I S G S 1 100 G I N I S G S F C 1 108 C R N K L K
Y L A 1 111 K L K Y L A F L H 1 119 H K R M N T N P S 1 132 H F Q V
P S R I F 1 136 P S R I F W R Q E 1 140 F W R Q E K A D G 1 142 R Q
E K A D G G S 1 143 Q E K A D G G S C 1 144 E K A D G G S C C 1 149
G S C C P Q G H A 1 151 C C P Q G H A S E 1 163 K V C L S G A P H 1
170 P H E V G W K Y Q 1 171 H E V G W K Y Q A 1 195 H Y R K N K Q L
M 1 198 K N K Q L M R L Q 1 201 Q L M R L Q K Q A 1 221 T E S P G G
G S P 1 249 R I G H P G G R T 1 255 G R T P R A G S S 1 256 R T P R
A G S S A 1 261 G S S A H R P P A 1 284 W L P L R T P W T 1 291 W T
R P S S C P T 1 295 S S C P T S S S T 1 298 P T S S S T Y D S 1 301
S S T Y D S L S P 1 303 T Y D S L S P Y G 1 309 P Y G P R N P L P 1
315 P L P N P R H S P 1 317 P N P R H S P S G 1 320 R H S P S G G G
G 1 343 V L A R G K P Q R 1 349 P Q R K P K S E N 1 350 Q R K P K S
E N N 1 356 E N N S W Y V E N 1 363 E N G R P A D L A 1 380 W K A I
E S L E E 1 387 E E G L G G K Q K 1
[0835]
42TABLE XXXV SEQ. Pos 1 2 3 4 5 6 7 8 9 0 score ID NO. 151P3D4 v.1:
HLA Peptide Scoring Results A1 10-mers SYFPEITHI 91 E V D V F V S M
G Y 25 263 Y L I H P T K L T Y 24 253 F T S N F N G R F Y 23 96 V S
M G Y H K K T Y 21 117 G S D S D A S L V I 21 292 I F A A W K I L G
Y 21 254 T S N F N G R F Y Y 20 64 Y R D P T A F G S G 19 119 D S D
A S L V I T D 19 33 Q A E N G P H L L V 18 186 A V I A S F D Q L Y
18 327 P T E A A V R F V G 18 344 L Y G V Y C F R A Y 18 138 K C E
V I E G L E D 17 336 G F P D K K H K L Y 17 337 F P D K K H K L Y G
17 125 V I T D L T L E D Y 16 126 I T D L T L E D Y G 16 128 D L T
L E D Y G R Y 16 154 L D L Q G V V F P Y 16 161 F P Y F P R L G R Y
16 181 C L D Q D A V I A S 16 229 Q N T V P G V R N Y 16 339 D K K
H K L Y G V Y 16 13 C W A D H L S D N Y 15 23 T L D H D R A I H I
15 55 G N V T L P C K F Y 15 79 I K W T K L T S D Y 15 99 G Y H K K
T Y G G Y 15 208 G W L S D G S V Q Y 15 210 L S D G S V Q Y P I 15
222 P R E P C G G Q N T 15 239 G F W D K D K S R Y 15 307 G W L A D
G S V R Y 15 18 L S D N Y T L D H D 14 25 D H D R A I H I Q A 14 57
V T L P C K F Y R D 14 85 T S D Y L K E V D V 14 130 T L E D Y G R
Y K C 14 272 Y D E A V Q A C L N 14 89 L K E V D V F V S M 13 144 G
L E D D T V V V A 13 146 E D D T V V V A L D 13 153 A L D L Q G V V
F P 13 174 F H E A Q Q A C L D 13 194 L Y D A W R G G L D 13 247 R
Y D V F C F T S N 13 280 L N D G A Q I A K V 13 107 G Y Q G R V F L
K G 12 141 V I E G L E D D T V 12 190 S F D Q L Y D A W R 12 309 L
A D G S V R Y P I 12 2 K S L L L L V L I S 11 41 L V E A E Q A K V
F 11 43 E A E Q A K V F S H 11 67 P T A F G S G I H K 11 122 A S L
V I T D L T L 11 145 L E D D T V V V A L 11 201 G L D W C N A G W L
11 230 N T V P G V R N Y G 11 240 F W D K D K S R Y D 11 242 D K D
K S R Y D V F 11 14 W A D H L S D N Y T 10 131 L E D Y G R Y K C E
10 183 D Q D A V I A S F D 10 219 I T K P R E P C G G 10 271 T Y D
E A V Q A C L 10 300 G Y D R C D A G W L 10 303 R C D A G W L A D G
10 22 Y T L D H D R A I H 9 34 A E N G P H L L V E 9 72 S G I H K I
R I K W 9 195 Y D A W R G G L D W 9 318 I S R P R R R C S P 9 11 S
I C W A D H L S D 8 81 W T K L T S D Y L K 8 82 T K L T S D Y L K E
8 148 D T V V V A L D L Q 8 160 V F P Y F P R L G R 8 165 P R L G R
Y N L N F 8 3 S L L L L V L I S I 7 17 H L S D N Y T L D H 7 52 H R
G G N V T L P C 7 84 L T S D Y L K E V D 7 103 K T Y G G Y Q G R V
7 129 L T L E D Y G R Y K 7 159 V V F P Y F P R L G 7 187 V I A S F
D Q L Y D 7 245 K S R Y D V F C F T 7 257 F N G R F Y Y L I H 7 270
L T Y D E A V Q A C 7 335 V G F P D K K H K L 7 10 I S I C W A D H
L S 6 50 F S H R G G N V T L 6 51 S H R G G N V T L P 6 70 F G S G
I H K I R I 6 77 I R I K W T K L T S 6 124 L V I T D L T L E D 6
147 D D T V V V A L D L 6 149 T V V V A L D L Q G 6 175 H E A Q Q A
C L D Q 6 203 D W C N A G W L S D 6 213 G S V Q Y P I T K P 6 267 P
T K L T Y D E A V 6 273 D E A V Q A C L N D 6 291 Q I F A A W K I L
G 6 302 D R C D A G W L A D 6 314 V R Y P I S R P R R 6 5 L L L V L
I S I C W 5 88 Y L K E V D V F V S 5 123 S L V I T D L T L E 5 135
G R Y K C E V I E G 5 155 D L Q G V V F P Y F 5 162 P Y F P R L G R
Y N 5 189 A S F D Q L Y D A W 5 215 V Q Y P I T K P R E 5 255 S N F
N G R F Y Y L 5 279 C L N D G A Q I A K 5 287 A K V G Q I F A A W 5
301 Y D R C D A G W L A 5 324 R C S P T E A A V R 5 35 E N G P H L
L V E A 4 44 A E Q A K V F S H R 4 71 G S G I H K I R I K 4 86 S D
Y L K E V D V F 4 137 Y K C E V I E G L E 4 212 D G S V Q Y P I T K
4 251 F C F T S N F N G R 4 258 N G R F Y Y L I H P 4 262 Y Y L I H
P T K L T 4 264 L I H P T K L T Y D 4 285 Q I A K V G Q I F A 4 311
D G S V R Y P I S R 4 312 G S V R Y P I S R P 4 325 C S P T E A A V
R F 4 331 A V R F V G F P D K 4 40 L L V E A E Q A K V 3 49 V F S H
R G G N V T 3 68 T A F G S G I H K I 3 94 V F V S M G Y H K K 3 95
F V S M G Y H K K T 3 100 Y H K K T Y G G Y Q 3 104 T Y G G Y Q G R
V F 3 105 Y G G Y Q G R V F L 3 106 G G Y Q G R V F L K 3 113 F L K
G G S D S D A 3 152 V A L D L Q G V V F 3 158 G V V F P Y F P R L 3
163 Y F P R L G R Y N L 3 164 F P R L G R Y N L N 3 168 G R Y N L N
F H E A 3 185 D A V I A S F D Q L 3 202 L D W C N A G W L S 3 207 A
G W L S D G S V Q 3 217 Y P I T K P R E P C 3 224 E P C G G Q N T V
P 3 234 G V R N Y G F W D K 3 235 V R N Y G F W D K D 3 256 N F N G
R F Y Y L I 3 261 F Y Y L I H P T K L 3 289 V G Q I F A A W K I 3
306 A G W L A D G S V R 3 316 Y P I S R P R R R C 3 326 S P T E A A
V R F V 3 328 T E A A V R F V G F 3 332 V R F V G F P D K K 3 333 R
F V G F P D K K H 3 345 Y G V Y C F R A Y N 3 1 M K S L L L L V L I
2 8 V L I S I C W A D H 2 15 A D H L S D N Y T L 2 16 D H L S D N Y
T L D 2 19 S D N Y T L D H D R 2 32 I Q A E N G P H L L 2 47 A K V
F S H R G G N 2 54 G G N V T L P C K F 2 75 H K I R I K W T K L 2
76 K I R I K W T K L T 2 90 K E V D V F V S M G 2 97 S M G Y H K K
T Y G 2 108 Y Q G R V F L K G G 2 116 G G S D S D A S L V 2 118 S D
S D A S L V I T 2 120 S D A S L V I T D L 2 121 D A S L V I T D L T
2 134 Y G R Y K C E V I E 2 151 V V A L D L Q G V V 2 170 Y N L N F
H E A Q Q 2 193 Q L Y D A W R G G L 2 197 A W R G G L D W C N 2 209
W L S D G S V Q Y P 2 211 S D G S V Q Y P I T 2 214 S V Q Y P I T K
P R 2 231 T V P G V R N Y G F 2 237 N Y G F W D K D K S 2 238 Y G F
W D K D K S R 2 246 S R Y D V F C F T S 2 248 Y D V F C F T S N F 2
250 V F C F T S N F N G 2 275 A V Q A C L N D G A 2 284 A Q I A K V
G Q I F 2 294 A A W K I L G Y D R 2 297 K I L G Y D R C D A 2 308 W
L A D G S V R Y P 2 313 S V R Y P I S R P R 2 319 S R P R R R C S P
T 2 330 A A V R F V G F P D 2 343 K L Y G V Y C F R A 2 4 L L L L V
L I S I C 1 6 L L V L I S I C W A 1 29 A I H I Q A E N G P 1 30 I H
I Q A E N G P H 1 31 H I Q A E N G P H L 1 36 N G P H L L V E A E 1
39 H L L V E A E Q A K 1 42 V E A E Q A K V F S 1 48 K V F S H R G
G N V 1 58 T L P C K F Y R D P 1 59 L P C K F Y R D P T 1 63 F Y R
D P T A F G S 1 65 R D P T A F G S G I 1 69 A F G S G I H K I R 1
83 K L T S D Y L K E V 1 92 V D V F V S M G Y H 1 93 D V F V S M G
Y H K 1 101 H K K T Y G G Y Q G 1 110 G R V F L K G G S D 1 111 R V
F L K G G S D S 1 112 V F L K G G S D S D 1 114 L K G G S D S D A S
1 132 E D Y G R Y K C E V 1 133 D Y G R Y K C E V I 1 142 I E G L E
D D T V V 1 143 E G L E D D T V V V 1 150 V V V A L D L Q G V 1 166
R L G R Y N L N F H 1 167 L G R Y N L N F H E 1 171 N L N F H E A Q
Q A 1 177 A Q Q A C L D Q D A 1 179 Q A C L D Q D A V I 1 180 A C L
D Q D A V I A 1 191 F D Q L Y D A W R G 1 198 W R G G L D W C N A 1
200 G G L D W C N A G W 1 205 C N A G W L S D G S 1 221 K P R E P C
G G Q N 1 225 P C G G Q N T V P G 1 226 C G G Q N T V P G V 1 227 G
G Q N T V P G V R 1 228 G Q N T V P G V R N 1 232 V P G V R N Y G F
W 1 233 P G V R N Y G F W D 1 236 R N Y G F W D K D K 1 241 W D K D
K S R Y D V 1 244 D K S R Y D V F C F 1 252 C F T S N F N G R F 1
268 T K L T Y D E A V Q 1 269 K L T Y D E A V Q A 1 276 V Q A C L N
D G A Q 1 277 Q A C L N D G A Q I 1 278 A C L N D G A Q I A 1 281 N
D G A Q I A K V G 1 283 G A Q I A K V G Q I 1 293 F A A W K I L G Y
D 1 295 A W K I L G Y D R C 1 298 I L G Y D R C D A G 1 304 C D A G
W L A D G S 1 310 A D G S V R Y P I S 1 317 P I S R P R R R C S 1
329 E A A V R F V G F P 1 334 F V G F P D K K H K 1 340 K K H K L Y
G V Y C 1 341 K H K L Y G V Y C F 1 151P3D4 v.2: HLA Peptide
Scoring Results A1 10-mers SYFPEITHI 68 S N D G E H W T V Y 29 105
G S F C R N K L K Y 27 295 S S C P T S S S T Y 25 58 Q F V G S Y K
L A Y 22 301 S S T Y D S L S P Y 21 187 K R K E K A E I H Y 19 220
Y T E S P G G G S P 19 30 K Q D K K V D L L V 18 168 G A P H E V G
W K Y 18 54 F G H V Q F V G S Y 17 211 K N M K K K I D K Y 17 7 K T
F P L R A L H I 16 122 M N T N P S R R P Y 16 152 C P Q G H A S E A
Y 16 352 K P K S E N N S W Y 16 366 R P A D L A G S G Y 16 385 S L
E E G L G G K Q 16 157 A S E A Y K K V C L 15 354 K S E N N S W Y V
E 15 77 Y Q D E K Q R K D K 13 97 S C E G I N I S G S 13 183 T L E
E K R K E K A 13 382 A I E S L E E G L G 13 4 H T T K T F P L R A
12 34 K V D L L V P T K V 12 51 A K D F G H V Q F V 12 78 Q D E K Q
R K D K V 12 208 Q A E K N M K K K I 12 300 S S S T Y D S L S P 12
322 S P S G G G G L K K 12 361 Y V E N G R P A D L 12 386 L E E G L
G G K Q K 12 1 M L E H T T K T F P 11 17 V V E S I R D H S G 11 21
I R D H S G Q K M K 11 70 D G E H W T V Y Q D 11 123 N T N P S R R
P Y H 11 142 R Q E K A D G G S C 11 145 K A D G G S C C P Q 11 191
K A E I H Y R K N K 11 278 A A S P A A W L P L 11 40 P T K V T G I
I T Q 10 83 R K D K V L L G R K 10 96 V S C E G I N I S G 10 111 K
L K Y L A F L H K 10 127 S R R P Y H F Q V P 10 170 P H E V G W K Y
Q A 10 184 L E E K R K E K A E 10 188 R K E K A E I H Y R 10 216 K
I D K Y T E S P G 10 228 S P R G L G F I F K 10 291 W T R P S S C P
T S 10 303 T Y D S L S P Y G P 10 309 P Y G P R N P L P N 10 367 P
A D L A G S G Y C 10 372 G S G Y C G A L W K 10 394 Q K D K E R K A
E N 10 396 D K E R K A E N G P 10 81 K Q R K D K V L L G 9 177 Y Q
A V T A T L E E 8 182 A T L E E K R K E K 8 262 S S A H R P P A L S
8 263 S A H R P P A L S A 8 280 S P A A W L P L R T 8 302 S T Y D S
L S P Y G 8 31 Q D K K V D L L V P 7 43 V T G I I T Q G A K 7 47 I
T Q G A K D F G H 7 103 I S G S F C R N K L 7 167 S G A P H E V G W
K 7 180 V T A T L E E K R K 7 195 H Y R K N K Q L M R 7 198 K N K Q
L M R L Q K 7 225 G G G S P R G L G F 7 244 A T R A T R I G H P 7
247 A T R I G H P G G R 7 279 A S P A A W L P L R 7 306 S L S P Y G
P R N P 7 321 H S P S G G G G L K 7 323 P S G G G G L K K P 7 337 Q
G Q K H N V L A R 7 383 I E S L E E G L G G 7 5 T T K T F P L R A L
6 9 F P L R A L H I V V 6 37 L L V P T K V T G I 6 39 V P T K V T G
I I T 6 67 Y S N D G E H W T V 6 74 W T V Y Q D E K Q R 6 82 Q R K
D K V L L G R 6 94 V V V S C E G I N I 6 108 C R N K L K Y L A F 6
150 S C C P Q G H A S E 6 159 E A Y K K V C L S G 6 235 I F K T I A
P L A A 6 237 K T I A P L A A T R 6 243 A A T R A T R I G H 6 256 R
T P R A G S S A H 6 288 R T P W T R P S S C 6 298 P T S S S T Y D S
L 6 299 T S S S T Y D S L S 6 308 S P Y G P R N P L P 6 346 R G K P
Q R K P K S 6 363 E N G R P A D L A G 6 379 L W K A I E S L E E 6 3
E H T T K T F P L R 5 20 S I R D H S G Q K M 5 104 S G S F C R N K
L K 5 132 H F Q V P S R I F W 5 133 F Q V P S R I F W R 5 136 P S R
I F W R Q E K 5 149 G S C C P Q G H A S 5 158 S E A Y K K V C L S 5
221 T E S P G G G S P R 5 222 E S P G G G S P R G 5 227 G S P R G L
G F I F 5 250 I G H P G G R T P R 5 255 G R T P R A G S S A 5 264 A
H R P P A L S A R 5 270 L S A R A P V P A A 5 272 A R A P V P A A S
P 5 274 A P V P A A S P A A 5 283 A W L P L R T P W T 5 287 L R T P
W T R P S S 5 305 D S L S P Y G P R N 5 307 L S P Y G P R N P L 5
312 P R N P L P N P R H 5 314 N P L P N P R H S P 5 320 R H S P S G
G G G L 5 358 N S W Y V E N G R P 5 371 A G S G Y C G A L W 5 14 L
H I V V E S I R D 4 19 E S I R D H S G Q K 4 24 H S G Q K M K Q D K
4 25 S G Q K M K Q D K K 4 61 G S Y K L A Y S N D 4 87 V L L G R K
A V V V 4 114 Y L A F L H K R M N 4 126 P S R R P Y H F Q V 4 137 S
R I F W R Q E K A 4 166 L S G A P H E V G W 4 210 E K N M K K K I D
K 4 224 P G G G S P R G L G 4 226 G G S P R G L G F I 4 230 R G L G
F I F K T I 4 232 L G F I F K T I A P 4 238 T I A P L A A T R A 4
261 G S S A H R P P A L 4 265 H R P P A L S A R A 4 294 P S S C P T
S S S T 4 316 L P N P R H S P S G 4 329 L K K P A R H C Q G 4 350 Q
R K P K S E N N S 4 362 V E N G R P A D L A 4 364 N G R P A D L A G
S 4 373 S G Y C G A L W K A 4 376 C G A L W K A I E S 4 378 A L W K
A I E S L E 4 384 E S L E E G L G G K 4 389 G L G G K Q K D K E 4 6
T K T F P L R A L H 3 29 M K Q D K K V D L L 3 44 T G I I T Q G A K
D 3 48 T Q G A K D F G H V 3 53 D F G H V Q F V G S 3 57 V Q P V G
S Y K L A 3 63 Y K L A Y S N D G E 3 76 V Y Q D E K Q R K D 3 84 K
D K V L L G R K A 3 88 L L G R K A V V V S 3 101 I N I S G S F C R
N 3 107 F C R N K L K Y L A 3 117 F L H K R M N T N P 3 134 Q V P S
R I F W R Q 3 165 C L S G A P H E V G 3 179 A V T A T L E E K R 3
192 A E I H Y R K N K Q 3 206 Q K Q A E K N M K K 3 223 S P G G G S
P R G L 3 234 F I F K T I A P L A 3 324 S G G G G L K K P A 3 332 P
A R H C Q G Q K H 3 336 C Q G Q K H N V L A 3 340 K H N V L A R G K
P 3 344 L A R G K P Q R K P 3 359 S W Y V E N G R P A 3 10 P L R A
L H I V V E 2 13 A L H I V V E S I R 2 22 R D H S G Q K M K Q 2 26
G Q K M K Q D K K V 2 35 V D L L V P T K V T 2 49 Q G A K D F G H V
Q 2 52 K D F G H V Q F V G 2 56 H V Q F V G S Y K L 2 62 S Y K L A
Y S N D G 2 73 H W T V Y Q D E K Q 2 80 E K Q R K D K V L L 2 106 S
F C R N K L K Y L 2 110 N K L K Y L A F L H 2 112 L K Y L A F L H K
R 2 131 Y H F Q V P S R I F 2 146 A D G G S C C P Q G 2 154 Q G H A
S E A Y K K 2 155 G H A S E A Y K K V 2 161 Y K K V C L S G A P 2
176 K Y Q A V T A T L E 2 181 T A T L E E K R K E 2 190 E K A E I H
Y R K N 2 194 I H Y R K N K Q L M 2 196 Y R K N K Q L M R L 2 197 R
K N K Q L M R L Q 2 199 N K Q L M R L Q K Q 2 203 M R L Q K Q A E K
N 2 207 K Q A E K N M K K K 2 229 P R G L G F I F K T 2 240 A P L A
A T R A T R 2 248 T R I G H P G G R T 2 260 A G S S A H R P P A 2
269 A L S A R A P V P A 2 271 S A R A P V P A A S 2 277 P A A S P A
A W L P 2 282 A A W L P L R T P W 2 296 S C P T S S S T Y D 2 304 Y
D S L S P Y G P R 2 310 Y G P R N P L P N P 2 328 G L K K P A R H C
Q 2 335 H C Q G Q K H N V L 2 343 V L A R G K P Q R K 2 345 A R G K
P Q R K P K 2 355 S E N N S W Y V E N 2 368 A D L A G S G Y C G 2
369 D L A G S G Y C G A 2 375 Y C G A L W K A I E 2 387 E E G L G G
K Q K D 2 392 G K Q K D K E R K A 2 399 R K A E N G P H L L 2 11 L
R A L H I V V E S 1 12 R A L H I V V E S I 1 16 I V V E S I R D H S
1 18 V E S I R D H S G Q 1 23 D H S G Q K M K Q D 1 27 Q K M K Q D
K K V D 1 33 K K V D L L V P T K 1 36 D L L V P T K V T G 1 42 K V
T G I I T Q G A 1 55 G H V Q F V G S Y K 1 59 F V G S Y K L A Y S 1
60 V G S Y K L A Y S N 1 64 K L A Y S N D G E H 1 65 L A Y S N D G
E H W 1 66 A Y S N D G E H W T 1 79 D E K Q R K D K V L 1 85 D K V
L L G R K A V 1 86 K V L L G R K A V V 1 89 L G R K A V V V S C 1
90 G R K A V V V S C E 1 93 A V V V S C E G I N 1 95 V V S C E G I
N I S 1 99 E G I N I S G S F C 1 102 N I S G S F C R N K 1 115 L A
F L H K R M N T 1 116 A F L H K R M N T N 1 119 H K R M N T N P S R
1 129 R P Y H F Q V P S R 1 135 V P S R I F W R Q E 1 140 F W R Q E
K A D G G 1 143 Q E K A D G G S C C 1 156 H A S E A Y K K V C 1 160
A Y K K V C L S G A 1 162 K K V C L S G A P H 1 164 V C L S G A P H
E V 1 169 A P H E V G W K Y Q 1 171 H E V G W K Y Q A V 1 172 E V G
W K Y Q A V T 1 173 V G W K Y Q A V T A 1 174 G W K Y Q A V T A T 1
193 E I H Y R K N K Q L 1 201 Q L M R L Q K Q A E 1 204 R L Q K Q A
E K N M 1 205 L Q K Q A E K N M K 1 209 A E K N M K K K I D 1 219 K
Y T E
S P G G G S 1 231 G L G F I F K T I A 1 236 F K T I A P L A A T 1
241 P L A A T R A T R I 1 245 T R A T R I G H P G 1 249 R I G H P G
G R T P 1 251 G H P G G R T P R A 1 252 H P G G R T P R A G 1 253 P
G G R T P R A G S 1 258 P R A G S S A H R P 1 267 P P A L S A R A P
V 1 268 P A L S A R A P V P 1 276 V P A A S P A A W L 1 284 W L P L
R T P W T R 1 286 P L R T P W T R P S 1 315 P L P N P R H S P S 1
319 P R H S P S G G G G 1 325 G G G G L K K P A R 1 333 A R H C Q G
Q K H N 1 341 H N V L A R G K P Q 1 351 R K P K S E N N S W 1 356 E
N N S W Y V E N G 1 360 W Y V E N G R P A D 1 374 G Y C G A L W K A
I 1 388 E G L G G K Q K D K 1 393 K Q K D K E R K A E 1 397 K E R K
A E N G P H 1 398 E R K A E N G P H L 1
[0836]
43TABLE XXXVI SEQ. Pos 1 2 3 4 5 6 7 8 9 0 score ID NO. 151P3D4
v.1: HLA Peptide Scoring Results A*0201 10-mers SYFPEITHI 3 S L L L
L V L I S I 28 40 L L V E A E Q A K V 28 83 K L T S D Y L K E V 25
193 Q L Y D A W R G G L 23 68 T A F G S G I H K I 22 141 V I E G L
E D D T V 22 280 L N D G A Q I A K V 22 144 G L E D D T V V V A 21
201 G L D W C N A G W L 21 6 L L V L I S I C W A 20 9 L I S I C W A
D H L 20 145 L E D D T V V V A L 20 150 V V V A L D L Q G V 20 31 H
I Q A E N G P H L 19 4 L L L L V L I S I C 18 23 T L D H D R A I H
I 18 103 K T Y G G Y Q G R V 18 120 S D A S L V I T D L 18 153 A L
D L Q G V V F P 18 343 K L Y G V Y C F R A 18 32 I Q A E N G P H L
L 17 88 Y L K E V D V F V S 17 122 A S L V I T D L T L 17 151 V V A
L D L Q G V V 17 263 Y L I H P T K L T Y 17 283 G A Q I A K V G Q I
17 297 K I L G Y D R C D A 17 308 W L A D G S V R Y P 17 309 L A D
G S V R Y P I 17 326 S P T E A A V R F V 17 335 V G F P D K K H K L
17 48 K V F S H R G G N V 16 73 G I H K I R I K W T 16 113 F L K G
G S D S D A 16 123 S L V I T D L T L E 16 206 N A G W L S D G S V
16 226 C G G Q N T V P G V 16 264 L I H P T K L T Y D 16 8 V L I S
I C W A D H 15 15 A D H L S D N Y T L 15 50 F S H R G G N V T L 15
115 K G G S D S D A S L 15 158 G V V F P Y F P R L 15 166 R L G R Y
N L N F H 15 181 C L D Q D A V I A S 15 209 W L S D G S V Q Y P 15
269 K L T Y D E A V Q A 15 305 D A G W L A D G S V 15 1 M K S L L L
L V L I 14 5 L L L V L I S I C W 14 33 Q A E N G P H L L V 14 75 H
K I R I K W T K L 14 136 R Y K C E V I E G L 14 171 N L N F H E A Q
Q A 14 173 N F H E A Q Q A C L 14 179 Q A C L D Q D A V I 14 188 I
A S F D Q L Y D A 14 255 S N F N G R F Y Y L 14 261 F Y Y L I H P T
K L 14 271 T Y D E A V Q A C L 14 277 Q A C L N D G A Q I 14 285 Q
I A K V G Q I F A 14 286 I A K V G Q I F A A 14 11 S I C W A D H L
S D 13 39 H L L V E A E Q A K 13 78 R I K W T K L T S D 13 87 D Y L
K E V D V F V 13 105 Y G G Y Q G R V F L 13 118 S D S D A S L V I T
13 125 V I T D L T L E D Y 13 130 T L E D Y G R Y K C 13 143 E G L
E D D T V V V 13 163 Y F P R L G R Y N L 13 178 Q Q A C L D Q D A V
13 185 D A V I A S F D Q L 13 210 L S D G S V Q Y P I 13 223 R E P
C G G Q N T V 13 270 L T Y D E A V Q A C 13 279 C L N D G A Q I A K
13 323 R R C S P T E A A V 13 17 H L S D N Y T L D H 12 29 A I H I
Q A E N G P 12 76 K I R I K W T K L T 12 116 G G S D S D A S L V 12
132 E D Y G R Y K C E V 12 142 I E G L E D D T V V 12 155 D L Q G V
V F P Y F 12 187 V I A S F D Q L Y D 12 256 N F N G R F Y Y L I 12
298 I L G Y D R C D A G 12 338 P D K K H K L Y G V 12 22 Y T L D H
D R A I H 11 35 E N G P H L L V E A 11 70 F G S G I H K I R I 11 85
T S D Y L K E V D V 11 124 L V I T D L T L E D 11 180 A C L D Q D A
V I A 11 182 L D Q D A V I A S F 11 241 W D K D K S R Y D V 11 267
P T K L T Y D E A V 11 275 A V Q A C L N D G A 11 289 V G Q I F A A
W K I 11 290 G Q I F A A W K I L 11 293 F A A W K I L G Y D 11 300
G Y D R C D A G W L 11 34 A E N G P H L L V E 10 57 V T L P C K F Y
R D 10 58 T L P C K F Y R D P 10 80 K W T K L T S D Y L 10 95 F V S
M G Y H K K T 10 117 G S D S D A S L V I 10 129 L T L E D Y G R Y K
10 152 V A L D L Q G V V F 10 259 G R F Y Y L I H P T 10 292 I F A
A W K I L G Y 10 7 L V L I S I C W A D 9 14 W A D H L S D N Y T 9
65 R D P T A F G S G I 9 89 L K E V D V F V S M 9 97 S M G Y H K K
T Y G 9 140 E V I E G L E D D T 9 147 D D T V V V A L D L 9 168 G R
Y N L N F H E A 9 291 Q I F A A W K I L G 9 2 K S L L L L V L I S 8
21 N Y T L D H D R A I 8 24 L D H D R A I H I Q 8 51 S H R G G N V
T L P 8 128 D L T L E D Y G R Y 8 135 G R Y K C E V I E G 8 154 L D
L Q G V V F P Y 8 159 V V F P Y F P R L G 8 186 A V I A S F D Q L Y
8 196 D A W R G G L D W C 8 219 I T K P R E P C G G 8 231 T V P G V
R N Y G F 8 278 A C L N D G A Q I A 8 294 A A W K I L G Y D R 8 12
I C W A D H L S D N 7 42 V E A E Q A K V F S 7 77 I R I K W T K L T
S 7 84 L T S D Y L K E V D 7 86 S D Y L K E V D V F 7 121 D A S L V
I T D L T 7 133 D Y G R Y K C E V I 7 148 D T V V V A L D L Q 7 200
G G L D W C N A G W 7 211 S D G S V Q Y P I T 7 213 G S V Q Y P I T
K P 7 230 N T V P G V R N Y G 7 262 Y Y L I H P T K L T 7 287 A K V
G Q I F A A W 7 288 K V G Q I F A A W K 7 299 L G Y D R C D A G W 7
329 E A A V R F V G F P 7 18 L S D N Y T L D H D 6 28 R A I H I Q A
E N G 6 43 E A E Q A K V F S H 6 49 V F S H R G G N V T 6 59 L P C
K F Y R D P T 6 64 Y R D P T A F G S G 6 72 S G I H K I R I K W 6
90 K E V D V F V S M G 6 106 G G Y Q G R V F L K 6 107 G Y Q G R V
F L K G 6 108 Y Q G R V F L K G G 6 126 I T D L T L E D Y G 6 170 Y
N L N F H E A Q Q 6 177 A Q Q A C L D Q D A 6 198 W R G G L D W C N
A 6 246 S R Y D V F C F T S 6 274 E A V Q A C L N D G 6 301 Y D R C
D A G W L A 6 303 R C D A G W L A D G 6 318 I S R P R R R C S P 6
319 S R P R R R C S P T 6 330 A A V R F V G F P D 6 331 A V R F V G
F P D K 6 10 I S I C W A D H L S 5 26 H D R A I H I Q A E 5 27 D R
A I H I Q A E N 5 36 N G P H L L V E A E 5 37 G P H L L V E A E Q 5
53 R G G N V T L P C K 5 71 G S G I H K I R I K 5 82 T K L T S D Y
L K E 5 93 D V F V S M G Y H K 5 96 V S M G Y H K K T Y 5 111 R V F
L K G G S D S 5 112 V F L K G G S D S D 5 114 L K G G S D S D A S 5
119 D S D A S L V I T D 5 149 T V V V A L D L Q G 5 161 F P Y F P R
L G R Y 5 176 E A Q Q A C L D Q D 5 189 A S F D Q L Y D A W 5 195 Y
D A W R G G L D W 5 204 W C N A G W L S D G 5 205 C N A G W L S D G
S 5 208 G W L S D G S V Q Y 5 215 V Q Y P I T K P R E 5 218 P I T K
P R E P C G 5 234 G V R N Y G F W D K 5 249 D V F C F T S N F N 5
253 F T S N F N G R F Y 5 266 H P T K L T Y D E A 5 304 C D A G W L
A D G S 5 307 G W L A D G S V R Y 5 312 G S V R Y P I S R P 5 313 S
V R Y P I S R P R 5 314 V R Y P I S R P R R 5 317 P I S R P R R R C
S 5 322 R R R C S P T E A A 5 328 T E A A V R F V G F 5 341 K H K L
Y G V Y C F 5 20 D N Y T L D H D R A 4 30 I H I Q A E N G P H 4 41
L V E A E Q A K V F 4 46 Q A K V F S H R G G 4 54 G G N V T L P C K
F 4 62 K F Y R D P T A F G 4 81 W T K L T S D Y L K 4 94 V F V S M
G Y H K K 4 127 T D L T L E D Y G R 4 137 Y K C E V I E G L E 4 139
C E V I E G L E D D 4 172 L N F H E A Q Q A C 4 190 S F D Q L Y D A
W R 4 197 A W R G G L D W C N 4 214 S V Q Y P I T K P R 4 217 Y P I
T K P R E P C 4 228 G Q N T V P G V R N 4 238 Y G F W D K D K S R 4
245 K S R Y D V F C F T 4 251 F C F T S N F N G R 4 268 T K L T Y D
E A V Q 4 276 V Q A C L N D G A Q 4 282 D G A Q I A K V G Q 4 284 A
Q I A K V G Q I F 4 316 Y P I S R P R R R C 4 324 R C S P T E A A V
R 4 332 V R F V G F P D K K 4 13 C W A D H L S D N Y 3 19 S D N Y T
L D H D R 3 25 D H D R A I H I Q A 3 38 P H L L V E A E Q A 3 52 H
R G G N V T L P C 3 56 N V T L P C K F Y R 3 63 F Y R D P T A F G S
3 74 I H K I R I K W T K 3 79 I K W T K L T S D Y 3 98 M G Y H K K
T Y G G 3 134 Y G R Y K C E V I E 3 138 K C E V I E G L E D 3 146 E
D D T V V V A L D 3 156 L Q G V V F P Y F P 3 175 H E A Q Q A C L D
Q 3 202 L D W C N A G W L S 3 207 A G W L S D G S V Q 3 221 K P R E
P C G G Q N 3 229 Q N T V P G V R N Y 3 235 V R N Y G F W D K D 3
239 G F W D K D K S R Y 3 244 D K S R Y D V F C F 3 258 N G R F Y Y
L I H P 3 260 R F Y Y L I H P T K 3 265 I H P T K L T Y D E 3 306 A
G W L A D G S V R 3 310 A D G S V R Y P I S 3 320 R P R R R C S P T
E 3 321 P R R R C S P T E A 3 333 R F V G F P D K K H 3 334 F V G F
P D K K H K 3 340 K K H K L Y G V Y C 3 344 L Y G V Y C F R A Y 3
345 Y G V Y C F R A Y N 3 44 A E Q A K V F S H R 2 47 A K V F S H R
G G N 2 60 P C K F Y R D P T A 2 67 P T A F G S G I H K 2 91 E V D
V F V S M G Y 2 99 G Y H K K T Y G G Y 2 104 T Y G G Y Q G R V F 2
110 G R V F L K G G S D 2 160 V F P Y F P R L G R 2 164 F P R L G R
Y N L N 2 165 P R L G R Y N L N F 2 169 R Y N L N F H E A Q 2 184 Q
D A V I A S F D Q 2 194 L Y D A W R G G L D 2 199 R G G L D W C N A
G 2 203 D W C N A G W L S D 2 216 Q Y P I T K P R E P 2 222 P R E P
C G G Q N T 2 236 R N Y G F W D K D K 2 243 K D K S R Y D V F C 2
247 R Y D V F C F T S N 2 257 F N G R F Y Y L I H 2 273 D E A V Q A
C L N D 2 296 W K I L G Y D R C D 2 302 D R C D A G W L A D 2 325 C
S P T E A A V R F 2 337 F P D K K H K L Y G 2 16 D H L S D N Y T L
D 1 61 C K F Y R D P T A F 1 69 A F G S G I H K I R 1 100 Y H K K T
Y G G Y Q 1 109 Q G R V F L K G G S 1 167 L G R Y N L N F H E 1 191
F D Q L Y D A W R G 1 192 D Q L Y D A W R G G 1 212 D G S V Q Y P I
T K 1 220 T K P R E P C G G Q 1 225 P C G G Q N T V P G 1 227 G G Q
N T V P G V R 1 232 V P G V R N Y G F W 1 237 N Y G F W D K D K S 1
240 F W D K D K S R Y D 1 248 Y D V F C F T S N F 1 272 Y D E A V Q
A C L N 1 295 A W K I L G Y D R C 1 311 D G S V R Y P I S R 1 336 G
F P D K K H K L Y 1 342 H K L Y G V Y C F R 1 183 D Q D A V I A S F
D -1 224 E P C G G Q N T V P -1 242 D K D K S R Y D V F -1 252 C F
T S N F N G R F -1 281 N D G A Q I A K V G -1 66 D P T A F G S G I
H -2 339 D K K H K L Y G V Y -2 233 P G V R N Y G F W D -3 151P3D4
v.2: HLA Peptide Scoring Results A*0201 10-mers SYFPEITHI 37 L L V
P T K V T G I 27 87 V L L G R K A V V V 27 377 G A L W K A I E S L
23 12 R A L H I V V E S I 20 28 K M K Q D K K V D L 20 381 K A I E
S L E E G L 20 86 K V L L G R K A V V 19 278 A A S P A A W L P L 19
5 T T K T F P L R A L 18 88 L L G R K A V V V S 18 233 G F I F K T
I A P L 18 269 A L S A R A P V P A 18 369 D L A G S G Y C G A 18 7
K T F P L R A L H I 17 20 S I R D H S G Q K M 17 34 K V D L L V P T
K V 17 183 T L E E K R K E K A 17 241 P L A A T R A T R I 17 361 Y
V E N G R P A D L 17 370 L A G S G Y C G A L 17 56 H V Q F V G S Y
K L 16 67 Y S N D G E H W T V 16 164 V C L S G A P H E V 16 238 T I
A P L A A T R A 16 8 T F P L R A L H I V 15 29 M K Q D K K V D L L
15 36 D L L V P T K V T G 15 51 A K D F G H V Q F V 15 103 I S G S
F C R N K L 15 106 S F C R N K L K Y L 15 109 R N K L K Y L A F L
15 175 W K Y Q A V T A T L 15 196 Y R K N K Q L M R L 15 223 S P G
G G S P R G L 15 226 G G S P R G L G F I 15 234 F I F K T I A P L A
15 276 V P A A S P A A W L 15 385 S L E E G L G G K Q 15 389 G L G
G K Q K D K E 15 399 R K A E N G P H L L 15 38 L V P T K V T G I I
14 64 K L A Y S N D G E H 14 92 K A V V V S C E G I 14 155 G H A S
E A Y K K V 14 202 L M R L Q K Q A E K 14 231 G L G F I F K T I A
14 270 L S A R A P V P A A 14 306 S L S P Y G P R N P 14 9 F P L R
A L H I V V 13 10 P L R A L H I V V E 13 94 V V V S C E G I N I 13
114 Y L A F L H K R M N 13 157 A S E A Y K K V C L 13 171 H E V G W
K Y Q A V 13 193 E I H Y R K N K Q L 13 204 R L Q K Q A E K N M 13
230 R G L G F I F K T I 13 261 G S S A H R P P A L 13 263 S A H R P
P A L S A 13 298 P T S S S T Y D S L 13 320 R H S P S G G G G L 13
335 H C Q G Q K H N V L 13 343 V L A R G K P Q R K 13 373 S G Y C G
A L W K A 13 378 A L W K A I E S L E 13 2 L E H T T K T F P L 12 11
L R A L H I V V E S 12 13 A L H I V V E S I R 12 15 H I V V E S I R
D H 12 30 K Q D K K V D L L V 12 165 C L S G A P H E V G 12 201 Q L
M R L Q K Q A E 12 208 Q A E K N M K K K I 12 284 W L P L R T P W T
R 12 307 L S P Y G P R N P L 12 26 G Q K M K Q D K K V 11 42 K V T
G I I T Q G A 11 59 F V G S Y K L A Y S 11 78 Q D E K Q R K D K V
11 115 L A F L H K R M N T 11 117 F L H K R M N T N P 11 182 A T L
E E K R K E K 11 236 F K T I A P L A A T 11 237 K T I A P L A A T R
11 239 I A P L A A T R A T 11 267 P P A L S A R A P V 11 283 A W L
P L R T P W T 11 328 G L K K P A R H C Q 11 334 R H C Q G Q K H N V
11 374 G Y C G A L W K A I 11 45 G I I T Q G A K D F 10 48 T Q G A
K D F G H V 10 89 L G R K A V V V S C 10 95 V V S C E G I N I S 10
100 G I N I S G S F C R 10 102 N I S G S F C R N K 10 111 K L K Y L
A F L H K 10 112 L K Y L A F L H K R 10 160 A Y K K V C L S G A 10
167 S G A P H E V G W K 10 173 V G W K Y Q A V T A 10 178 Q A V T A
T L E E K 10 212 N M K K K I D K Y T 10 244 A T R A T R I G H P 10
249 R I G H P G G R T P 10 272 A R A P V P A A S P 10 274 A P V P A
A S P A A 10 344 L A R G K P Q R K P 10 1 M L E H T T K T F P 9 33
K K V D L L V P T K 9 46 I I T Q G A K D F G 9 47 I T Q G A K D F G
H 9 80 E K Q R K D K V L L 9 85 D K V L L G R K A V 9 121 R M N T N
P S R R P 9 137 S R I F W R Q E K A 9 138 R I F W R Q E K A D 9 216
K I D K Y T E S P G 9 264 A H R P P A L S A R 9 271 S A R A P V P A
A S 9 280 S P A A W L P L R T 9 281 P A A W L P L R T P 9 291 W T R
P S S C P T S 9 302 S T Y D S L S P Y G 9 353 P K S E N N S W Y V 9
364 N G R P A D L A G S 9 382 A I E S L E E G L G 9 4 H T T K T F P
L R A 8 16 I V V E S I R D H S 8 32 D K K V D L L V P T 8 97 S C E
G I N I S G S 8 123 N T N P S R R P Y H 8 129 R P Y H F Q V P S R 8
150 S C C P Q G H A S E 8 174 G W K Y Q A V T A T 8 185 E E K R K E
K A E I 8 211 K N M K K K I D K Y 8 240 A P L A A T R A T R 8 242 L
A A T R A T R I G 8 248 T R I G H P G G R T 8 251 G H P G G R T P R
A 8 255 G R T P R A G S S A 8 265 H R P P A L S A R A 8 273 R A P V
P A A S P A 8 316 L P N P R H S P S G 8 362 V E N G R P A D L A 8
380 W K A I E S L E E G 8 17 V V E S I R D H S G 7 50 G A K D F G H
V Q F 7 54 F G H V Q F V G S Y 7 65 L A Y S N D G E H W 7 66 A Y S
N D G E H W T 7 79 D E K Q R K D K V L 7 116 A F L H K R M N T N 7
126 P S R R P Y H F Q V 7 133 F Q V P S R I F W R 7 145 K A D G G S
C C P Q 7 158 S E A Y K K V C L S 7 168 G A P H E V G W K Y 7 172 E
V G W K Y Q A V T 7 177 Y Q A V T A T L E E 7 179 A V T A T L E E K
R 7 192 A E I H Y R K N K Q 7 194 I H Y R K N K Q L M 7 220 Y T E S
P G G G S P 7 229 P R G L G F I F K T 7 235 I F K T I A P L A A 7
247 A T R I G H P G G R 7 260 A G S S A H R P P A 7 279 A S P A A W
L P L R 7 282 A A W L P L R T P W 7 286 P L R T P W T R P S 7 310 Y
G P R N P L P N P 7 314 N P L P N P R H S P 7 315 P L P N P R H S P
S 7 322 S P S G G G G L K K 7 324 S G G G G L K K P A 7 342 N V L A
R G K P Q R 7 355 S E N N S W Y V E N 7 359 S W Y V E N G R P A 7
392 G K Q K D K E R K A 7 398 E R K A E N G P H L 7 35 V D L L V P
T K V T 6 40 P T K V T G I I T Q 6 43 V T G I I T Q G A K 6 44 T G
I I T Q G A K D 6 81 K Q R K D K V L L G 6 82 Q R K D K V L L G R 6
84 K D K V L L G R K A 6 93 A V V V S C E G I N 6 107 F C R N K L K
Y L A 6 113 K Y L A F L H K R M 6 151 C C P Q G H A S E A 6 163 K V
C L S G A P H E 6 180 V T A T L E E K R K 6 199 N K Q L M R L Q K Q
6 200 K Q L M R L Q K Q A 6 207 K Q A E K N M K K K 6 215 K K I D K
Y T E S P 6 243 A A T R A T R I G H 6 262 S S A H R P P A L S 6 287
L R T P W T R P S S 6 288 R T P W T R P S S C 6 295 S S C P T S S S
T Y 6 308 S P Y G P R N P L P 6 336 C Q G Q K H N V L A 6 337 Q G Q
K H N V L A R 6 338 G Q K H N V L A R G 6 371 A G S G Y C G A L W 6
384 E S L E E G L G G K 6 57 V Q F V G S Y K L A 5 63 Y K L A Y S N
D G E 5 75 T V Y Q D E K Q R K 5 96 V S C E G I N I S G 5 105 G S F
C R N K L K Y 5 139 I F W R Q E K A D G 5 146 A D G G S C C P Q G 5
148 G G S C C P Q G H A 5
156 H A S E A Y K K V C 5 159 E A Y K K V C L S G 5 166 L S G A P H
E V G W 5 181 T A T L E E K R K E 5 246 R A T R I G H P G G 5 256 R
T P R A G S S A H 5 300 S S S T Y D S L S P 5 325 G G G G L K K P A
R 5 368 A D L A G S G Y C G 5 14 L H I V V E S I R D 4 25 S G Q K M
K Q D K K 4 31 Q D K K V D L L V P 4 39 V P T K V T G I I T 4 41 T
K V T G I I T Q G 4 52 K D F G H V Q F V G 4 58 Q F V G S Y K L A Y
4 68 S N D G E H W T V Y 4 69 N D G E H W T V Y Q 4 76 V Y Q D E K
Q R K D 4 83 R K D K V L L G R K 4 90 G R K A V V V S C E 4 91 R K
A V V V S C E G 4 101 I N I S G S F C R N 4 127 S R R P Y H F Q V P
4 130 P Y H F Q V P S R I 4 134 Q V P S R I F W R Q 4 188 R K E K A
E I H Y R 4 203 M R L Q K Q A E K N 4 228 S P R G L G F I F K 4 232
L G F I F K T I A P 4 250 I G H P G G R T P R 4 259 R A G S S A H R
P P 4 268 P A L S A R A P V P 4 275 P V P A A S P A A W 4 285 L P L
R T P W T R P 4 301 S S T Y D S L S P Y 4 323 P S G G G G L K K P 4
340 K H N V L A R G K P 4 346 R G K P Q R K P K S 4 360 W Y V E N G
R P A D 4 366 R P A D L A G S G Y 4 375 Y C G A L W K A I E 4 376 C
G A L W K A I E S 4 379 L W K A I E S L E E 4 383 I E S L E E G L G
G 4 394 Q K D K E R K A E N 4 49 Q G A K D F G H V Q 3 60 V G S Y K
L A Y S N 3 70 D G E H W T V Y Q D 3 77 Y Q D E K Q R K D K 3 108 C
R N K L K Y L A F 3 119 H K R M N T N P S R 3 131 Y H F Q V P S R I
F 3 141 W R Q E K A D G G S 3 149 G S C C P Q G H A S 3 152 C P Q G
H A S E A Y 3 154 Q G H A S E A Y K K 3 162 K K V C L S G A P H 3
169 A P H E V G W K Y Q 3 190 E K A E I H Y R K N 3 191 K A E I H Y
R K N K 3 219 K Y T E S P G G G S 3 225 G G G S P R G L G F 3 245 T
R A T R I G H P G 3 252 H P G G R T P R A G 3 254 G G R T P R A G S
S 3 277 P A A S P A A W L P 3 294 P S S C P T S S S T 3 326 G G G L
K K P A R H 3 327 G G L K K P A R H C 3 329 L K K P A R H C Q G 3
331 K P A R H C Q G Q K 3 332 P A R H C Q G Q K H 3 348 K P Q R K P
K S E N 3 351 R K P K S E N N S W 3 365 G R P A D L A G S G 3 390 L
G G K Q K D K E R 3 18 V E S I R D H S G Q 2 22 R D H S G Q K M K Q
2 53 D F G H V Q F V G S 2 61 G S Y K L A Y S N D 2 62 S Y K L A Y
S N D G 2 74 W T V Y Q D E K Q R 2 98 C E G I N I S G S F 2 110 N K
L K Y L A F L H 2 118 L H K R M N T N P S 2 120 K R M N T N P S R R
2 140 F W R Q E K A D G G 2 161 Y K K V C L S G A P 2 187 K R K E K
A E I H Y 2 205 L Q K Q A E K N M K 2 206 Q K Q A E K N M K K 2 213
M K K K I D K Y T E 2 214 K K K I D K Y T E S 2 217 I D K Y T E S P
G G 2 221 T E S P G G G S P R 2 257 T P R A G S S A H R 2 258 P R A
G S S A H R P 2 292 T R P S S C P T S S 2 293 R P S S C P T S S S 2
296 S C P T S S S T Y D 2 303 T Y D S L S P Y G P 2 304 Y D S L S P
Y G P R 2 305 D S L S P Y G P R N 2 311 G P R N P L P N P R 2 330 K
K P A R H C Q G Q 2 347 G K P Q R K P K S E 2 350 Q R K P K S E N N
S 2 356 E N N S W Y V E N G 2 357 N N S W Y V E N G R 2 386 L E E G
L G G K Q K 2 395 K D K E R K A E N G 2 21 I R D H S G Q K M K 1 55
G H V Q F V G S Y K 1 71 G E H W T V Y Q D E 1 73 H W T V Y Q D E K
Q 1 124 T N P S R R P Y H F 1 125 N P S R R P Y H F Q 1 128 R R P Y
H F Q V P S 1 135 V P S R I F W R Q E 1 142 R Q E K A D G G S C 1
170 P H E V G W K Y Q A 1 176 K Y Q A V T A T L E 1 184 L E E K R K
E K A E 1 189 K E K A E I H Y R K 1 195 H Y R K N K Q L M R 1 197 R
K N K Q L M R L Q 1 198 K N K Q L M R L Q K 1 218 D K Y T E S P G G
G 1 227 G S P R G L G F I F 1 266 R P P A L S A R A P 1 289 T P W T
R P S S C P 1 312 P R N P L P N P R H 1 318 N P R H S P S G G G 1
333 A R H C Q G Q K H N 1 339 Q K H N V L A R G K 1 345 A R G K P Q
R K P K 1 354 K S E N N S W Y V E 1 367 P A D L A G S G Y C 1 372 G
S G Y C G A L W K 1 393 K Q K D K E R K A E 1 397 K E R K A E N G P
H 1 19 E S I R D H S G Q K -1 99 E G I N I S G S F C -1 122 M N T N
P S R R P Y -1 136 P S R I F W R Q E K -1 143 Q E K A D G G S C C
-1 153 P Q G H A S E A Y K -1 224 P G G G S P R G L G -1 341 H N V
L A R G K P Q -1 363 E N G R P A D L A G -1 387 E E G L G G K Q K D
-1 210 E K N M K K K I D K -2 317 P N P R H S P S G G -2 319 P R H
S P S G G G G -2 3 E H T T K T F P L R -3 186 E K R K E K A E I H
-3 349 P Q R K P K S E N N -3
[0837]
44TABLE XXXVII SEQ. Pos 1 2 3 4 5 6 7 8 9 0 score ID NO. 151P3D4
v.1: HLA Peptide Scoring Results A*0202 10-mers SYFPEITHI 293 F A A
W K I L G Y D 5 329 E A A V R F V G F P 5 13 C W A D H L S D N Y 3
27 D R A I H I Q A E N 3 32 I Q A E N G P H L L 3 42 V E A E Q A K
V F S 3 45 E Q A K V F S H R G 3 67 P T A F G S G I H K 3 120 S D A
S L V I T D L 3 151 V V A L D L Q G V V 3 175 H E A Q Q A C L D Q 3
178 Q Q A C L D Q D A V 3 184 Q D A V I A S F D Q 3 187 V I A S F D
Q L Y D 3 195 Y D A W R G G L D W 3 205 C N A G W L S D G S 3 273 D
E A V Q A C L N D 3 276 V Q A C L N D G A Q 3 282 D G A Q I A K V G
Q 3 285 Q I A K V G Q I F A 3 292 I F A A W K I L G Y 3 294 A A W K
I L G Y D R 3 304 C D A G W L A D G S 3 308 W L A D G S V R Y P 3
328 T E A A V R F V G F 3 330 A A V R F V G F P D 3 14 W A D H L S
D N Y T 2 28 R A I H I Q A E N G 2 33 Q A E N G P H L L V 2 43 E A
E Q A K V F S H 2 46 Q A K V F S H R G G 2 68 T A F G S G I H K I 2
121 D A S L V I T D L T 2 152 V A L D L Q G V V F 2 176 E A Q Q A C
L D Q D 2 179 Q A C L D Q D A V I 2 185 D A V I A S F D Q L 2 188 I
A S F D Q L Y D A 2 196 D A W R G G L D W C 2 206 N A G W L S D G S
V 2 274 E A V Q A C L N D G 2 277 Q A C L N D G A Q I 2 283 G A Q I
A K V G Q I 2 286 I A K V G Q I F A A 2 305 D A G W L A D G S V 2
309 L A D G S V R Y P I 2 15 A D H L S D N Y T L 1 29 A I H I Q A E
N G P 1 34 A E N G P H L L V E 1 44 A E Q A K V F S H R 1 47 A K V
F S H R G G N 1 69 A F G S G I H K I R 1 122 A S L V I T D L T L 1
153 A L D L Q G V V F P 1 177 A Q Q A C L D Q D A 1 180 A C L D Q D
A V I A 1 186 A V I A S F D Q L Y 1 189 A S F D Q L Y D A W 1 197 A
W R G G L D W C N 1 207 A G W L S D G S V Q 1 275 A V Q A C L N D G
A 1 278 A C L N D G A Q I A 1 284 A Q I A K V G Q I F 1 287 A K V G
Q I F A A W 1 295 A W K I L G Y D R C 1 306 A G W L A D G S V R 1
310 A D G S V R Y P I S 1 331 A V R F V G F P D K 1 151P3D4 v.2:
HLA Peptide Scoring Results A*0202 10-mers SYFPEITHI 242 L A A T R
A T R I G 5 277 P A A S P A A W L P 5 281 P A A W L P L R T P 5 272
A R A P V P A A S P 4 11 L R A L H I V V E S 3 49 Q G A K D F G H V
Q 3 64 K L A Y S N D G E H 3 91 R K A V V V S C E G 3 114 Y L A F L
H K R M N 3 144 E K A D G G S C C P 3 155 G H A S E A Y K K V 3 158
S E A Y K K V C L S 3 167 S G A P H E V G W K 3 177 Y Q A V T A T L
E E 3 180 V T A T L E E K R K 3 190 E K A E I H Y R K N 3 207 K Q A
E K N M K K K 3 238 T I A P L A A T R A 3 241 P L A A T R A T R I 3
243 A A T R A T R I G H 3 245 T R A T R I G H P G 3 258 P R A G S S
A H R P 3 262 S S A H R P P A L S 3 267 P P A L S A R A P V 3 270 L
S A R A P V P A A 3 276 V P A A S P A A W L 3 278 A A S P A A W L P
L 3 280 S P A A W L P L R T 3 282 A A W L P L R T P W 3 331 K P A R
H C Q G Q K 3 343 V L A R G K P Q R K 3 366 R P A D L A G S G Y 3
369 D L A G S G Y C G A 3 376 C G A L W K A I E S 3 380 W K A I E S
L E E G 3 399 R K A E N G P H L L 3 12 R A L H I V V E S I 2 50 G A
K D F G H V Q F 2 65 L A Y S N D G E H W 2 92 K A V V V S C E G I 2
115 L A F L H K R M N T 2 145 K A D G G S C C P Q 2 156 H A S E A Y
K K V C 2 159 E A Y K K V C L S G 2 168 G A P H E V G W K Y 2 178 Q
A V T A T L E E K 2 181 T A T L E E K R K E 2 191 K A E I H Y R K N
K 2 208 Q A E K N M K K K I 2 239 I A P L A A T R A T 2 246 R A T R
I G H P G G 2 259 R A G S S A H R P P 2 263 S A H R P P A L S A 2
268 P A L S A R A P V P 2 271 S A R A P V P A A S 2 273 R A P V P A
A S P A 2 332 P A R H C Q G Q K H 2 344 L A R G K P Q R K P 2 367 P
A D L A G S G Y C 2 370 L A G S G Y C G A L 2 377 G A L W K A I E S
L 2 381 K A I E S L E E G L 2 13 A L H I V V E S I R 1 51 A K D F G
H V Q F V 1 66 A Y S N D G E H W T 1 93 A V V V S C E G I N 1 116 A
F L H K R M N T N 1 146 A D G G S C C P Q G 1 157 A S E A Y K K V C
L 1 160 A Y K K V C L S G A 1 169 A P H E V G W K Y Q 1 179 A V T A
T L E E K R 1 182 A T L E E K R K E K 1 192 A E I H Y R K N K Q 1
209 A E K N M K K K I D 1 240 A P L A A T R A T R 1 244 A T R A T R
I G H P 1 247 A T R I G H P G G R 1 260 A G S S A H R P P A 1 264 A
H R P P A L S A R 1 269 A L S A R A P V P A 1 274 A P V P A A S P A
A 1 279 A S P A A W L P L R 1 283 A W L P L R T P W T 1 333 A R H C
Q G Q K H N 1 345 A R G K P Q R K P K 1 368 A D L A G S G Y C G 1
371 A G S G Y C G A L W 1 378 A L W K A I E S L E 1 382 A I E S L E
E G L G 1
[0838]
45TABLE XXXVIII SEQ. Pos 1 2 3 4 5 6 7 8 9 0 score ID NO. 151P3D4
v.1: HLA Peptide Scoring Results A*0203 10-mers SYFPEITHI 286 I A K
V G Q I F A A 19 322 R R R C S P T E A A 19 287 A K V G Q I F A A W
17 323 R R C S P T E A A V 17 6 L L V L I S I C W A 10 20 D N Y T L
D H D R A 10 25 D H D R A I H I Q A 10 35 E N G P H L L V E A 10 38
P H L L V E A E Q A 10 60 P C K F Y R D P T A 10 113 F L K G G S D
S D A 10 144 G L E D D T V V V A 10 168 G R Y N L N F H E A 10 171
N L N F H E A Q Q A 10 177 A Q Q A C L D Q D A 10 180 A C L D Q D A
V I A 10 188 I A S F D Q L Y D A 10 198 W R G G L D W C N A 10 266
H P T K L T Y D E A 10 269 K L T Y D E A V Q A 10 275 A V Q A C L N
D G A 10 278 A C L N D G A Q I A 10 285 Q I A K V G Q I F A 10 297
K I L G Y D R C D A 10 301 Y D R C D A G W L A 10 321 P R R R C S P
T E A 10 343 K L Y G V Y C F R A 10 7 L V L I S I C W A D 9 21 N Y
T L D H D R A I 9 26 H D R A I H I Q A E 9 36 N G P H L L V E A E 9
39 H L L V E A E Q A K 9 61 C K F Y R D P T A F 9 114 L K G G S D S
D A S 9 145 L E D D T V V V A L 9 169 R Y N L N F H E A Q 9 172 L N
F H E A Q Q A C 9 178 Q Q A C L D Q D A V 9 181 C L D Q D A V I A S
9 189 A S F D Q L Y D A W 9 199 R G G L D W C N A G 9 267 P T K L T
Y D E A V 9 270 L T Y D E A V Q A C 9 276 V Q A C L N D G A Q 9 279
C L N D G A Q I A K 9 298 I L G Y D R C D A G 9 302 D R C D A G W L
A D 9 344 L Y G V Y C F R A Y 9 8 V L I S I C W A D H 8 22 Y T L D
H D R A I H 8 27 D R A I H I Q A E N 8 37 G P H L L V E A E Q 8 40
L L V E A E Q A K V 8 62 K F Y R D P T A F G 8 115 K G G S D S D A
S L 8 146 E D D T V V V A L D 8 170 Y N L N F H E A Q Q 8 173 N F H
E A Q Q A C L 8 179 Q A C L D Q D A V I 8 182 L D Q D A V I A S F 8
190 S F D Q L Y D A W R 8 200 G G L D W C N A G W 8 268 T K L T Y D
E A V Q 8 271 T Y D E A V Q A C L 8 277 Q A C L N D G A Q I 8 280 L
N D G A Q I A K V 8 288 K V G Q I F A A W K 8 299 L G Y D R C D A G
W 8 303 R C D A G W L A D G 8 324 R C S P T E A A V R 8 345 Y G V Y
C F R A Y N 8 151P3D4 v.2: HLA Peptide Scoring Results A*0203
10-mers SYFPEITHI 235 I F K T I A P L A A 19 270 L S A R A P V P A
A 19 274 A P V P A A S P A A 19 265 H R P P A L S A R A 18 236 F K
T I A P L A A T 17 271 S A R A P V P A A S 17 275 P V P A A S P A A
W 17 4 H T T K T F P L R A 10 42 K V T G I I T Q G A 10 57 V Q F V
G S Y K L A 10 84 K D K V L L G R K A 10 107 F C R N K L K Y L A 10
137 S R I F W R Q E K A 10 148 G G S C C P Q G H A 10 151 C C P Q G
H A S E A 10 160 A Y K K V C L S G A 10 170 P H E V G W K Y Q A 10
173 V G W K Y Q A V T A 10 183 T L E E K R K E K A 10 200 K Q L M R
L Q K Q A 10 231 G L G F I F K T I A 10 234 F I F K T I A P L A 10
238 T I A P L A A T R A 10 251 G H P G G R T P R A 10 255 G R T P R
A G S S A 10 260 A G S S A H R P P A 10 263 S A H R P P A L S A 10
269 A L S A R A P V P A 10 273 R A P V P A A S P A 10 324 S G G G G
L K K P A 10 336 C Q G Q K H N V L A 10 359 S W Y V E N G R P A 10
362 V E N G R P A D L A 10 369 D L A G S G Y C G A 10 373 S G Y C G
A L W K A 10 392 G K Q K D K E R K A 10 5 T T K T F P L R A L 9 43
V T G I I T Q G A K 9 58 Q F V G S Y K L A Y 9 85 D K V L L G R K A
V 9 108 C R N K L K Y L A F 9 138 R I F W R Q E K A D 9 149 G S C C
P Q G H A S 9 152 C P Q G H A S E A Y 9 161 Y K K V C L S G A P 9
171 H E V G W K Y Q A V 9 174 G W K Y Q A V T A T 9 184 L E E K R K
E K A E 9 201 Q L M R L Q K Q A E 9 232 L G F I F K T I A P 9 239 I
A P L A A T R A T 9 252 H P G G R T P R A G 9 256 R T P R A G S S A
H 9 261 G S S A H R P P A L 9 264 A H R P P A L S A R 9 266 R P P A
L S A R A P 9 325 G G G G L K K P A R 9 337 Q G Q K H N V L A R 9
360 W Y V E N G R P A D 9 363 E N G R P A D L A G 9 370 L A G S G Y
C G A L 9 374 G Y C G A L W K A I 9 393 K Q K D K E R K A E 9 6 T K
T F P L R A L H 8 44 T G I I T Q G A K D 8 59 F V G S Y K L A Y S 8
86 K V L L G R K A V V 8 109 R N K L K Y L A F L 8 139 I F W R Q E
K A D G 8 150 S C C P Q G H A S E 8 153 P Q G H A S E A Y K 8 162 K
K V C L S G A P H 8 172 E V G W K Y Q A V T 8 175 W K Y Q A V T A T
L 8 185 E E K R K E K A E I 8 202 L M R L Q K Q A E K 8 233 G F I F
K T I A P L 8 237 K T I A P L A A T R 8 240 A P L A A T R A T R 8
253 P G G R T P R A G S 8 257 T P R A G S S A H R 8 262 S S A H R P
P A L S 8 267 P P A L S A R A P V 8 272 A R A P V P A A S P 8 276 V
P A A S P A A W L 8 326 G G G L K K P A R H 8 338 G Q K H N V L A R
G 8 361 Y V E N G R P A D L 8 364 N G R P A D L A G S 8 371 A G S G
Y C G A L W 8 375 Y C G A L W K A I E 8 394 Q K D K E R K A E N
8
[0839]
46TABLE XXXIX SEQ. Pos 1 2 3 4 5 6 7 8 9 0 score ID NO. 151P3D4
v.1: HLA Peptide Scoring Results A3 10-mers SYFPEITHI 288 K V G Q I
F A A W K 30 263 Y L I H P T K L T Y 26 331 A V R F V G F P D K 26
186 A V I A S F D Q L Y 24 234 G V R N Y G F W D K 24 39 H L L V E
A E Q A K 23 41 L V E A E Q A K V F 23 93 D V F V S M G Y H K 23
269 K L T Y D E A V Q A 23 260 R F Y Y L I H P T K 22 279 C L N D G
A Q I A K 22 111 R V F L K G G S D S 21 166 R L G R Y N L N F H 21
324 R C S P T E A A V R 21 8 V L I S I C W A D H 20 236 R N Y G F W
D K D K 20 334 F V G F P D K K H K 20 144 G L E D D T V V V A 19
193 Q L Y D A W R G G L 19 343 K L Y G V Y C F R A 19 17 H L S D N
Y T L D H 18 74 I H K I R I K W T K 18 128 D L T L E D Y G R Y 18
152 V A L D L Q G V V F 18 153 A L D L Q G V V F P 18 306 A G W L A
D G S V R 18 313 S V R Y P I S R P R 18 48 K V F S H R G G N V 17
91 E V D V F V S M G Y 17 151 V V A L D L Q G V V 17 3 S L L L L V
L I S I 16 4 L L L L V L I S I C 16 78 R I K W T K L T S D 16 88 Y
L K E V D V F V S 16 113 F L K G G S D S D A 16 124 L V I T D L T L
E D 16 129 L T L E D Y G R Y K 16 149 T V V V A L D L Q G 16 155 D
L Q G V V F P Y F 16 171 N L N F H E A Q Q A 16 231 T V P G V R N Y
G F 16 297 K I L G Y D R C D A 16 53 R G G N V T L P C K 15 56 N V
T L P C K F Y R 15 76 K I R I K W T K L T 15 125 V I T D L T L E D
Y 15 201 G L D W C N A G W L 15 208 G W L S D G S V Q Y 15 212 D G
S V Q Y P I T K 15 214 S V Q Y P I T K P R 15 275 A V Q A C L N D G
A 15 284 A Q I A K V G Q I F 15 7 L V L I S I C W A D 14 11 S I C W
A D H L S D 14 40 L L V E A E Q A K V 14 67 P T A F G S G I H K 14
86 S D Y L K E V D V F 14 106 G G Y Q G R V F L K 14 140 E V I E G
L E D D T 14 141 V I E G L E D D T V 14 159 V V F P Y F P R L G 14
207 A G W L S D G S V Q 14 221 K P R E P C G G Q N 14 292 I F A A W
K I L G Y 14 307 G W L A D G S V R Y 14 320 R P R R R C S P T E 14
23 T L D H D R A I H I 13 31 H I Q A E N G P H L 13 62 K F Y R D P
T A F G 13 83 K L T S D Y L K E V 13 104 T Y G G Y Q G R V F 13 123
S L V I T D L T L E 13 180 A C L D Q D A V I A 13 298 I L G Y D R C
D A G 13 5 L L L V L I S I C W 12 6 L L V L I S I C W A 12 9 L I S
I C W A D H L 12 29 A I H I Q A E N G P 12 34 A E N G P H L L V E
12 44 A E Q A K V F S H R 12 77 I R I K W T K L T S 12 81 W T K L T
S D Y L K 12 96 V S M G Y H K K T Y 12 122 A S L V I T D L T L 12
130 T L E D Y G R Y K C 12 150 V V V A L D L Q G V 12 187 V I A S F
D Q L Y D 12 264 L I H P T K L T Y D 12 277 Q A C L N D G A Q I 12
291 Q I F A A W K I L G 12 308 W L A D G S V R Y P 12 314 V R Y P I
S R P R R 12 317 P I S R P R R R C S 12 339 D K K H K L Y G V Y 12
22 Y T L D H D R A I H 11 50 F S H R G G N V T L 11 71 G S G I H K
I R I K 11 79 I K W T K L T S D Y 11 143 E G L E D D T V V V 11 161
F P Y F P R L G R Y 11 165 P R L G R Y N L N F 11 181 C L D Q D A V
I A S 11 209 W L S D G S V Q Y P 11 227 G G Q N T V P G V R 11 285
Q I A K V G Q I F A 11 318 I S R P R R R C S P 11 325 C S P T E A A
V R F 11 328 T E A A V R F V G F 11 332 V R F V G F P D K K 11 28 R
A I H I Q A E N G 10 30 I H I Q A E N G P H 10 58 T L P C K F Y R D
P 10 65 R D P T A F G S G I 10 94 V F V S M G Y H K K 10 95 F V S M
G Y H K K T 10 103 K T Y G G Y Q G R V 10 158 G V V F P Y F P R L
10 179 Q A C L D Q D A V I 10 182 L D Q D A V I A S F 10 239 G F W
D K D K S R Y 10 246 S R Y D V F C F T S 10 249 D V F C F T S N F N
10 253 F T S N F N G R F Y 10 257 F N G R F Y Y L I H 10 294 A A W
K I L G Y D R 10 315 R Y P I S R P R R R 10 333 R F V G F P D K K H
10 340 K K H K L Y G V Y C 10 2 K S L L L L V L I S 9 38 P H L L V
E A E Q A 9 73 G I H K I R I K W T 9 138 K C E V I E G L E D 9 170
Y N L N F H E A Q Q 9 190 S F D Q L Y D A W R 9 268 T K L T Y D E A
V Q 9 278 A C L N D G A Q I A 9 281 N D G A Q I A K V G 9 287 A K V
G Q I F A A W 9 303 R C D A G W L A D G 9 330 A A V R F V G F P D 9
341 K H K L Y G V Y C F 9 13 C W A D H L S D N Y 8 15 A D H L S D N
Y T L 8 90 K E V D V F V S M G 8 115 K G G S D S D A S L 8 142 I E
G L E D D T V V 8 154 L D L Q G V V F P Y 8 160 V F P Y F P R L G R
8 183 D Q D A V I A S F D 8 197 A W R G G L D W C N 8 218 P I T K P
R E P C G 8 223 R E P C G G Q N T V 8 229 Q N T V P G V R N Y 8 242
D K D K S R Y D V F 8 243 K D K S R Y D V F C 8 299 L G Y D R C D A
G W 8 300 G Y D R C D A G W L 8 321 P R R R C S P T E A 8 322 R R R
C S P T E A A 8 323 R R C S P T E A A V 8 12 I C W A D H L S D N 7
35 E N G P H L L V E A 7 49 V F S H R G G N V T 7 51 S H R G G N V
T L P 7 61 C K F Y R D P T A F 7 63 F Y R D P T A F G S 7 66 D P T
A F G S G I H 7 69 A F G S G I H K I R 7 75 H K I R I K W T K L 7
99 G Y H K K T Y G G Y 7 101 H K K T Y G G Y Q G 7 102 K K T Y G G
Y Q G R 7 116 G G S D S D A S L V 7 117 G S D S D A S L V I 7 133 D
Y G R Y K C E V I 7 134 Y G R Y K C E V I E 7 195 Y D A W R G G L D
W 7 215 V Q Y P I T K P R E 7 219 I T K P R E P C G G 7 224 E P C G
G Q N T V P 7 228 G Q N T V P G V R N 7 233 P G V R N Y G F W D 7
244 D K S R Y D V F C F 7 247 R Y D V F C F T S N 7 248 Y D V F C F
T S N F 7 254 T S N F N G R F Y Y 7 261 F Y Y L I H P T K L 7 311 D
G S V R Y P I S R 7 319 S R P R R R C S P T 7 327 P T E A A V R F V
G 7 336 G F P D K K H K L Y 7 344 L Y G V Y C F R A Y 7 25 D H D R
A I H I Q A 6 26 H D R A I H I Q A E 6 33 Q A E N G P H L L V 6 42
V K A E Q A K V F S 6 43 E A E Q A K V F S H 6 55 G N V T L P C K F
Y 6 64 Y R D P T A F G S G 6 87 D Y L K E V D V F V 6 89 L K E V D
V F V S M 6 109 Q G R V F L K G G S 6 110 G R V F L K G G S D 6 118
S D S D A S L V I T 6 119 D S D A S L V I T D 6 127 T D L T L E D Y
G R 6 132 E D Y G R Y K C E V 6 145 L E D D T V V V A L 6 147 D D T
V V V A L D L 6 157 Q G V V F P Y F P R 6 162 P Y F P R L G R Y N 6
169 R Y N L N F H E A Q 6 194 L Y D A W R G G L D 6 199 R G G L D W
C N A G 6 200 G G L D W C N A G W 6 203 D W C N A G W L S D 6 222 P
R E P C G G Q N T 6 225 P C G G Q N T V P G 6 238 Y G F W D K D K S
R 6 245 K S R Y D V F C F T 6 270 L T Y D E A V Q A C 6 301 Y D R C
D A G W L A 6 304 C D A G W L A D G S 6 312 G S V R Y P I S R P 6
342 H K L Y G V Y C F R 6 1 M K S L L L L V L I 5 10 I S I C W A D
H L S 5 19 S D N Y T L D H D R 5 27 D R A I H I Q A E N 5 32 I Q A
E N G P H L L 5 47 A K V F S H R G G N 5 52 H R G G N V T L P C 5
54 G G N V T L P C K F 5 57 V T L P C K F Y R D 5 60 P C K F Y R D
P T A 5 72 S G I H K I R I K W 5 82 T K L T S D Y L K E 5 84 L T S
D Y L K E V D 5 92 V D V F V S M G Y H 5 100 Y H K K T Y G G Y Q 5
105 Y G G Y Q G R V F L 5 107 G Y Q G R V F L K G 5 136 R Y K C E V
I E G L 5 168 G R Y N L N F H E A 5 174 F H E A Q Q A C L D 5 177 A
Q Q A C L D Q D A 5 189 A S F D Q L Y D A W 5 204 W C N A G W L S D
G 5 252 C F T S N F N G R F 5 272 Y D E A V Q A C L N 5 280 L N D G
A Q I A K V 5 282 D G A Q I A K V G Q 5 283 G A Q I A K V G Q I 5
295 A W K I L G Y D R C 5 302 D R C D A G W L A D 5 20 D N Y T L D
H D R A 4 37 G P H L L V E A E Q 4 85 T S D Y L K E V D V 4 98 M G
Y H K K T Y G G 4 112 V F L K G G S D S D 4 135 G R Y K C E V I E G
4 163 Y F P R L G R Y N L 4 164 F P R L G R Y N L N 4 173 N F H E A
Q Q A C L 4 175 H E A Q Q A C L D Q 4 178 Q Q A C L D Q D A V 4 185
D A V I A S F D Q L 4 191 F D Q L Y D A W R G 4 196 D A W R G G L D
W C 4 216 Q Y P I T K P R E P 4 217 Y P I T K P R E P C 4 220 T K P
R E P C G G Q 4 230 N T V P G V R N Y G 4 251 F C F T S N F N G R 4
271 T Y D E A V Q A C L 4 273 D E A V Q A C L N D 4 286 I A K V G Q
I F A A 4 289 V G Q I F A A W K I 4 296 W K I L G Y D R C D 4 316 Y
P I S R P R R R C 4 345 Y G V Y C F R A Y N 4 16 D H L S D N Y T L
D 3 46 Q A K V F S H R G G 3 80 K W T K L T S D Y L 3 108 Y Q G R V
F L K G G 3 114 L K G G S D S D A S 3 120 S D A S L V I T D L 3 126
I T D L T L E D Y G 3 146 E D D T V V V A L D 3 167 L G R Y N L N F
H E 3 176 E A Q Q A C L D Q D 3 184 Q D A V I A S F D Q 3 202 L D W
C N A G W L S 3 205 C N A G W L S D G S 3 206 N A G W L S D G S V 3
241 W D K D K S R Y D V 3 258 N G R F Y Y L I H P 3 262 Y Y L I H P
T K L T 3 267 P T K L T Y D E A V 3 276 V Q A C L N D G A Q 3 290 G
Q I F A A W K I L 3 305 D A G W L A D G S V 3 309 L A D G S V R Y P
I 3 310 A D G S V R Y P I S 3 335 V G F P D K K H K L 3 337 F P D K
K H K L Y G 3 21 N Y T L D H D R A I 2 68 T A F G S G I H K I 2 70
F G S G I H K I R I 2 97 S M G Y H K K T Y G 2 137 Y K C E V I E G
L E 2 188 I A S F D Q L Y D A 2 192 D Q L Y D A W R G G 2 198 W R G
G L D W C N A 2 210 L S D G S V Q Y P I 2 255 S N F N G R F Y Y L 2
256 N F N G R F Y Y L I 2 265 I H P T K L T Y D E 2 293 F A A W K I
L G Y D 2 326 S P T E A A V R F V 2 329 E A A V R F V G F P 2 18 L
S D N Y T L D H D 1 24 L D H D R A I H I Q 1 36 N G P H L L V E A E
1 45 E Q A K V F S H R G 1 59 L P C K F Y R D P T 1 121 D A S L V I
T D L T 1 139 C E V I E G L E D D 1 156 L Q G V V F P Y F P 1 172 L
N F H E A Q Q A C 1 211 S D G S V Q Y P I T 1 213 G S V Q Y P I T K
P 1 232 V P G V R N Y G F W 1 338 P D K K H K L Y G V 1 151P3D4
v.2: HLA Peptide Scoring Results A3 10-mers SYFPEITHI 111 K L K Y L
A F L H K 27 87 V L L G R K A V V V 25 343 V L A R G K P Q R K 25
75 T V Y Q D E K Q R K 24 10 P L R A L H I V V E 23 86 K V L L G R
K A V V 23 237 K T I A P L A A T R 22 13 A L H I V V E S I R 21 88
L L G R K A V V V S 21 198 K N K Q L M R L Q K 21 331 K P A R H C Q
G Q K 21 342 N V L A R G K P Q R 21 19 E S I R D H S G Q K 20 36 D
L L V P T K V T G 20 102 N I S G S F C R N K 20 269 A L S A R A P V
P A 20 284 W L P L R T P W T R 20 64 K L A Y S N D G E H 19 179 A V
T A T L E E K R 19 240 A P L A A T R A T R 19 249 R I G H P G G R T
P 19 322 S P S G G G G L K K 19 33 K K V D L L V P T K 18 45 G I I
T Q G A K D F 18 366 R P A D L A G S G Y 18 386 L E E G L G G K Q K
18 154 Q G H A S E A Y K K 17 163 K V C L S G A P H E 17 167 S G A
P H E V G W K 17 172 E V G W K Y Q A V T 17 182 A T L E E K R K E K
17 202 L M R L Q K Q A E K 17 241 P L A A T R A T R I 17 264 A H R
P P A L S A R 17 275 P V P A A S P A A W 17 295 S S C P T S S S T Y
17 372 G S G Y C G A L W K 17 20 S I R D H S G Q K M 16 34 K V D L
L V P T K V 16 55 G H V Q F V G S Y K 16 165 C L S G A P H E V G 16
189 K E K A E I H Y R K 16 201 Q L M R L Q K Q A E 16 228 S P R G L
G F I F K 16 238 T I A P L A A T R A 16 339 Q K H N V L A R G K 16
378 A L W K A I E S L E 16 385 S L E E G L G G K Q 16 42 K V T G I
I T Q G A 15 83 R K D K V L L G R K 15 136 P S R I F W R Q E K 15
191 K A E I H Y R K N K 15 206 Q K Q A E K N M K K 15 207 K Q A E K
N M K K K 15 256 R T P R A G S S A H 15 272 A R A P V P A A S P 15
306 S L S P Y G P R N P 15 361 Y V E N G R P A D L 15 16 I V V E S
I R D H S 14 37 L L V P T K V T G I 14 58 Q F V G S Y K L A Y 14 68
S N D G E H W T V Y 14 93 A V V V S C E G I N 14 129 R P Y H F Q V
P S R 14 204 R L Q K Q A E K N M 14 216 K I D K Y T E S P G 14 315
P L P N P R H S P S 14 321 H S P S G G G G L K 14 345 A R G K P Q R
K P K 14 352 K P K S E N N S W Y 14 384 E S L E E G L G G K 14 388
E G L G G K Q K D K 14 21 I R D H S G Q K M K 13 43 V T G I I T Q G
A K 13 50 G A K D F G H V Q F 13 59 F V G S Y K L A Y S 13 94 V V V
S C E G I N I 13 100 G I N I S G S F C R 13 138 R I F W R Q E K A D
13 153 P Q G H A S E A Y K 13 162 K K V C L S G A P H 13 221 T E S
P G G G S P R 13 247 A T R I G H P G G R 13 286 P L R T P W T R P S
13 369 D L A G S G Y C G A 13 7 K T F P L R A L H I 12 15 H I V V E
S I R D H 12 17 V V E S I R D H S G 12 77 Y Q D E K Q R K D K 12
114 Y L A F L H K R M N 12 120 K R M N T N P S R R 12 134 Q V P S R
I F W R Q 12 178 Q A V T A T L E E K 12 205 L Q K Q A E K N M K 12
230 R G L G F I F K T I 12 257 T P R A G S S A H R 12 263 S A H R P
P A L S A 12 328 G L K K P A R H C Q 12 382 A I E S L E E G L G 12
389 G L G G K Q K D K E 12 1 M L E H T T K T F P 11 25 S G Q K M K
Q D K K 11 38 L V P T K V T G I I 11 82 Q R K D K V L L G R 11 104
S G S F C R N K L K 11 117 F L H K R M N T N P 11 127 S R R P Y H F
Q V P 11 143 Q E K A D G G S C C 11 173 V G W K Y Q A V T A 11 175
W K Y Q A V T A T L 11 180 V T A T L E E K R K 11 183 T L E E K R K
E K A 11 187 K R K E K A E I H Y 11 193 E I H Y R K N K Q L 11 195
H Y R K N K Q L M R 11 231 G L G F I F K T I A 11 234 F I F K T I A
P L A 11 243 A A T R A T R I G H 11 250 I G H P G G R T P R 11 255
G R T P R A G S S A 11 271 S A R A P V P A A S 11 320 R H S P S G G
G G L 11 371 A G S G Y C G A L W 11 391 G G K Q K D K E R K 11 397
K E R K A E N G P H 11 24 H S G Q K M K Q D K 10 31 Q D K K V D L L
V P 10 44 T G I I T Q G A K D 10 46 I I T Q G A K D F G 10 49 Q G A
K D F G H V Q 10 56 H V Q F V G S Y K L 10 72 E H W T V Y Q D E K
10 95 V V S C E G I N I S 10 99 E G I N I S G S F C 10 142 R Q E K
A D G G S C 10 186 E K R K E K A E I H 10 210 E K N M K K K I D K
10 225 G G G S P R G L G F 10 227 G S P R G L G F I F 10 266 R P P
A L S A R A P 10 273 R A P V P A A S P A 10 276 V P A A S P A A W L
10 288 R T P W T R P S S C 10 291 W T R P S S C P T S 10 301 S S T
Y D S L S P Y 10 332 P A R H C Q G Q K H 10 337 Q G Q K H N V L A R
10 368 A D L A G S G Y C G 10 9 F P L R A L H I V V 9 52 K D F G H
V Q F V G 9 54 F G H V Q F V G S Y 9 81 K Q R K D K V L L G 9 89 L
G R K A V V V S C 9 105 G S F C R N K L K Y 9 109 R N K L K Y L A F
L 9 110 N K L K Y L A F L H 9 112 L K Y L A F L H K R 9 116 A F L H
K R M N T N 9 119 H K R M N T N P S R 9 126 P S R R P Y H F Q V 9
150 S C C P Q G H A S E 9 152 C P Q G H A S E A Y 9 157 A S E A Y K
K V C L 9 159 E A Y K K V C L S G 9 168 G A P H E V G W K Y 9 176 K
Y Q A V T A T L E 9 194 I H Y R K N K Q L M 9 211 K N M K K K I D K
Y 9 215 K K I D K Y T E S P 9 244 A T R A T R I G H P 9 248 T R I G
H P G G R T 9 254 G G R T P R A G S S 9 268 P A L S A R A P V P 9
278 A A S P A A W L P L 9 279 A S P A A W L P L R 9 283 A W L P L R
T P W T 9 293 R P S S C P T S S S 9 311 G P R N P L P N P R 9 326 G
G G L K K P A R H 9 348 K P Q R K P K S E N 9 364 N G R P A D L A G
S 9 383 I E S L E E G L G G 9 6 T K T F P L R A L H 8 12 R A L H I
V V E S I 8 28 K M K Q D K K V D L 8 47 I T Q G A K D F G H 8 98 C
E G I N I S G S F 8 108 C R N K L K Y L A F 8 122 M N T N P S R R P
Y 8 123 N T N P S R R P Y H 8 128 R R P Y H F Q V P S 8 133 F Q V P
S R I F W R 8 139 I F W R Q E K A D G 8 146 A D G G S C C P Q G 8
188 R K E K A E I H Y R 8 200 K Q L M R L Q K Q A 8 219 K Y T E S P
G G G S 8 235 I F K T I A P L A A 8 280 S P A A W L P L R T 8 314 N
P L P N P R H S P 8 346 R G K P Q R K P K S 8 354 K S E N N S W Y V
E 8 359 S W Y V E N G R P A 8 365 G R P A D L A G S G 8 395 K D K E
R K A E N G 8 35 V D L L V P T K V T 7 61 G S Y K L A Y S N D 7 65
L A Y S N D G E H W 7 74 W T V Y Q D E K Q R 7 80 E K Q R K D K V L
L 7 84 K D K V L L G R K A 7 113 K Y L A F L H K R M 7 160 A Y K K
V C L S G A 7 185 E E K R K E K A E I 7
246 R A T R I G H P G G 7 253 P G G R T P R A G S 7 274 A P V P A A
S P A A 7 308 S P Y G P R N P L P 7 309 P Y G P R N P L P N 7 312 P
R N P L P N P R H 7 317 P N P R H S P S G G 7 325 G G G G L K K P A
R 7 329 L K K P A R H C Q G 7 363 E N G R P A D L A G 7 381 K A I E
S L E E G L 7 393 K Q K D K E R K A E 7 399 R K A E N G P H L L 7
11 L R A L H I V V E S 6 27 Q K M K Q D K K V D 6 30 K Q D K K V D
L L V 6 90 G R K A V V V S C E 6 97 S C E G I N I S G S 6 135 V P S
R I F W R Q E 6 140 F W R Q E K A D G G 6 151 C C P Q G H A S E A 6
166 L S G A P H E V G W 6 192 A E I H Y R K N K Q 6 214 K K K I D K
Y T E S 6 218 D K Y T E S P G G G 6 220 Y T E S P G G G S P 6 233 G
F I F K T I A P L 6 258 P R A G S S A H R P 6 262 S S A H R P P A L
S 6 265 H R P P A L S A R A 6 267 P P A L S A R A P V 6 282 A A W L
P L R T P W 6 285 L P L R T P W T R P 6 287 L R T P W T R P S S 6
300 S S S T Y D S L S P 6 302 S T Y D S L S P Y G 6 304 Y D S L S P
Y G P R 6 313 R N P L P N P R H S 6 335 H C Q G Q K H N V L 6 350 Q
R K P K S E N N S 6 351 R K P K S E N N S W 6 355 S E N N S W Y V E
N 6 379 L W K A I E S L E E 6 398 E R K A E N G P H L 6 22 R D H S
G Q K M K Q 5 23 D H S G Q K M K Q D 5 32 D K K V D L L V P T 5 40
P T K V T G I I T Q 5 60 V G S Y K L A Y S N 5 66 A Y S N D G E H W
T 5 67 Y S N D G E H W T V 5 69 N D G E H W T V Y Q 5 79 D E K Q R
K D K V L 5 91 R K A V V V S C E G 5 101 I N I S G S F C R N 5 124
T N P S R R P Y H F 5 145 K A D G G S C C P Q 5 147 D G G S C C P Q
G H 5 156 H A S E A Y K K V C 5 203 M R L Q K Q A E K N 5 209 A E K
N M K K K I D 5 213 M K K K I D K Y T E 5 236 F K T I A P L A A T 5
270 L S A R A P V P A A 5 281 P A A W L P L R T P 5 294 P S S C P T
S S S T 5 305 D S L S P Y G P R N 5 316 L P N P R H S P S G 5 327 G
G L K K P A R H C 5 330 K K P A R H C Q G Q 5 340 K H N V L A R G K
P 5 344 L A R G K P Q R K P 5 362 V E N G R P A D L A 5 373 S G Y C
G A L W K A 5 375 Y C G A L W K A I E 5 376 C G A L W K A I E S 5
394 Q K D K E R K A E N 5 3 E H T T K T F P L R 4 4 H T T K T F P L
R A 4 18 V E S I R D H S G Q 4 41 T K V T G I I T Q G 4 53 D F G H
V Q F V G S 4 63 Y K L A Y S N D G E 4 106 S F C R N K L K Y L 4
107 F C R N K L K Y L A 4 118 L H K R M N T N P S 4 121 R M N T N P
S R R P 4 130 P Y H F Q V P S R I 4 131 Y H F Q V P S R I F 4 137 S
R I F W R Q E K A 4 149 G S C C P Q G H A S 4 169 A P H E V G W K Y
Q 4 177 Y Q A V T A T L E E 4 197 R K N K Q L M R L Q 4 223 S P G G
G S P R G L 4 224 P G G G S P R G L G 4 226 G G S P R G L G F I 4
239 I A P L A A T R A T 4 245 T R A T R I G H P G 4 252 H P G G R T
P R A G 4 259 R A G S S A H R P P 4 260 A G S S A H R P P A 4 261 G
S S A H R P P A L 4 277 P A A S P A A W L P 4 292 T R P S S C P T S
S 4 318 N P R H S P S G G G 4 319 P R H S P S G G G G 4 334 R H C Q
G Q K H N V 4 336 C Q G Q K H N V L A 4 338 G Q K H N V L A R G 4
341 H N V L A R G K P Q 4 357 N N S W Y V E N G R 4 377 G A L W K A
I E S L 4 390 L G G K Q K D K E R 4 14 L H I V V E S I R D 3 39 V P
T K V T G I I T 3 48 T Q G A K D F G H V 3 51 A K D F G H V Q F V 3
62 S Y K L A Y S N D G 3 70 D G E H W T V Y Q D 3 85 D K V L L G R
K A V 3 92 K A V V V S C E G I 3 96 V S C E G I N I S G 3 103 I S G
S F C R N K L 3 115 L A F L H K R M N T 3 125 N P S R R P Y H F Q 3
161 Y K K V C L S G A P 3 164 V C L S G A P H E V 3 170 P H E V G W
K Y Q A 3 171 H E V G W K Y Q A V 3 174 G W K Y Q A V T A T 3 196 Y
R K N K Q L M R L 3 217 I D K Y T E S P G G 3 289 T P W T R P S S C
P 3 290 P W T R P S S C P T 3 299 T S S S T Y D S L S 3 310 Y G P R
N P L P N P 3 324 S G G G G L K K P A 3 333 A R H C Q G Q K H N 3
347 G K P Q R K P K S E 3 349 P Q R K P K S E N N 3 360 W Y V E N G
R P A D 3 374 G Y C G A L W K A I 3 396 D K E R K A E N G P 3 5 T T
K T F P L R A L 2 78 Q D E K Q R K D K V 2 141 W R Q E K A D G G S
2 144 E K A D G G S C C P 2 158 S E A Y K K V C L S 2 190 E K A E I
H Y R K N 2 208 Q A E K N M K K K I 2 222 E S P G G G S P R G 2 232
L G F I F K T I A P 2 251 G H P G G R T P R A 2 296 S C P T S S S T
Y D 2 298 P T S S S T Y D S L 2 323 P S G G G G L K K P 2 367 P A D
L A G S G Y C 2 370 L A G S G Y C G A L 2 380 W K A I E S L E E G 2
8 T F P L R A L H I V 1 26 G Q K M K Q D K K V 1 29 M K Q D K K V D
L L 1 76 V Y Q D E K Q R K D 1 132 H F Q V P S R I F W 1 148 G G S
C C P Q G H A 1 155 G H A S E A Y K K V 1 181 T A T L E E K R K E 1
184 L E E K R K E K A E 1 199 N K Q L M R L Q K Q 1 212 N M K K K I
D K Y T 1 229 P R G L G F I F K T 1 242 L A A T R A T R I G 1 303 T
Y D S L S P Y G P 1 307 L S P Y G P R N P L 1 353 P K S E N N S W Y
V 1 358 N S W Y V E N G R P 1 387 E E G L G G K Q K D 1
[0840]
47TABLE XL SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4 v.1:
HLA Peptide Scoring Results A26 10-mers SYFPEITHI 155 D L Q G V V F
P Y F 31 91 E V D V F V S M G Y 29 128 D L T L E D Y G R Y 29 125 V
I T D L T L E D Y 25 158 G V V F P Y F P R L 24 231 T V P G V R N Y
G F 24 186 A V I A S F D Q L Y 23 242 D K D K S R Y D V F 22 292 I
F A A W K I L G Y 22 339 D K K H K L Y G V Y 21 31 H I Q A E N G P
H L 20 41 L V E A E Q A K V F 20 140 E V I E G L E D D T 20 148 D T
V V V A L D L Q 20 244 D K S R Y D V F C F 20 253 F T S N F N G R F
Y 20 263 Y L I H P T K L T Y 20 9 L I S I C W A D H L 19 93 D V F V
S M G Y H K 19 185 D A V I A S F D Q L 19 239 G F W D K D K S R Y
19 193 Q L Y D A W R G G L 18 249 D V F C F T S N F N 18 252 C F T
S N F N G R F 18 336 G F P D K K H K L Y 18 57 V T L P C K F Y R D
17 173 N F H E A Q Q A C L 17 182 L D Q D A V I A S F 17 201 G L D
W C N A G W L 17 270 L T Y D E A V Q A C 17 328 T E A A V R F V G F
17 78 R I K W T K L T S D 16 99 G Y H K K T Y G G Y 16 145 L E D D
T V V V A L 16 150 V V V A L D L Q G V 16 163 Y F P R L G R Y N L
16 264 L I H P T K L T Y D 16 73 G I H K I R I K W T 15 88 Y L K E
V D V F V S 15 154 L D L Q G V V F P Y 15 161 F P Y F P R L G R Y
15 181 C L D Q D A V I A c 15 229 Q N T V P G V R N Y 15 331 A V R
F V G F P D K 15 341 K H K L Y G V Y C F 15 344 L Y G V Y C F R A Y
15 35 E N G P H L L V E A 14 48 K V F S H R G G N V 14 83 K L T S D
Y L K E V 14 86 S D Y L K E V D V F 14 89 L K E V D V F V S M 14
120 S D A S L V I T D L 14 136 R Y K C E V I E G L 14 144 G L E D D
T V V V A 14 147 D D T V V V A L D L 14 153 A L D L Q G V V F P 14
159 V V F P Y F P R L G 14 209 W L S D G S V Q Y P 14 219 I T K P R
E P C G G 14 234 G V R N Y G F W D K 14 255 S N F N G R F Y Y L 14
308 W L A D G S V R Y P 14 3 S L L L L V L I S I 13 4 L L L L V L I
S I C 13 13 C W A D H L S D N Y 13 58 T L P C K F Y R D P 13 61 C K
F Y R D P T A F 13 103 K T Y G G Y Q G R V 13 111 R V F L K G G S D
S 13 124 L V I T D L T L E D 13 165 P R L G R Y N L N F 13 208 G W
L S D G S V Q Y 13 284 A Q I A K V G Q I F 13 325 C S P T E A A V R
F 13 335 V G F P D K K H K L 13 6 L L V L I S I C W A 12 8 V L I S
I C W A D H 12 22 Y T L D H D R A I H 12 40 L L V E A E Q A K V 12
43 E A E Q A K V F S H 12 67 P T A F G S G I H K 12 94 V F V S M G
Y H K K 12 96 V S M G Y H K K T Y 12 104 T Y G G Y Q G R V F 12 113
F L K G G S D S D A 12 123 S L V I T D L T L E 12 129 L T L E D Y G
R Y K 12 141 V I E G L E D D T V 12 146 E D D T V V V A L D 12 152
V A L D L Q G V V F 12 166 R L G R Y N L N F H 12 176 E A Q Q A C L
D Q D 12 187 V I A S F D Q L Y D 12 218 P I T K P R E P C G 12 230
N T V P G V R M Y G 12 248 Y D V F C F T S N F 12 256 N F N G R F Y
Y L I 12 267 P T K L T Y D E A V 12 271 T Y D E A V Q A C L 12 285
Q I A K V G Q I F A 12 288 K V G Q I F A A W K 12 291 Q I F A A W K
I L G 12 297 K I L G Y D R C D A 12 307 G W L A D G S V R Y 12 7 L
V L I S I C W A D 11 11 S I C W A D H L S D 11 16 D H L S D N Y T L
D 11 29 A I H I Q A E N G P 11 32 I Q A E N G P H L L 11 54 G G N V
T L P C K F 11 75 H K I R I K W T K L 11 79 I K W T K L T S D Y 11
81 W T K L T S D Y L K 11 84 L T S D Y L K E V D 11 95 F V S M G Y
H K K T 11 115 K G G S D S D A S L 11 119 D S D A S L V I T D 11
126 I T D L T L E D Y G 11 149 T V V V A L D L Q G 11 151 V V A L D
L Q G V V 11 274 E A V Q A C L N D G 11 275 A V Q A C L N D G A 11
329 E A A V R F V G F P 11 334 F V G F P D K K H K 11 343 K L Y G V
Y C F R A 11 23 T L D H D R A I H I 10 39 H L L V E A E Q A K 10 55
G N V T L P C K F Y 10 56 N V T L P C K F Y R 10 76 K I R I K W T K
L T 10 130 T L E D Y G R Y K C 10 171 N L N F H E A Q Q A 10 196 D
A W R G G L D W C 10 214 S V Q Y P I T K P R 10 254 T S N F N G R F
Y Y 10 269 K L T Y D E A V Q A 10 279 C L N D G A Q I A K 10 282 D
G A Q I A K V G Q 10 290 G Q I F A A W K I L 10 313 S V R Y P I S R
P R 10 317 P I S R P R R R C S 10 327 P T E A A V R F V G 10 17 H L
S D N Y T L D H 9 27 D R A I H I Q A E N 9 45 E Q A K V F S H R G 9
50 F S H R G G N V T L 9 68 T A F G S G I H K I 9 80 K W T K L T S
D Y L 9 105 Y G G Y Q G R V F L 9 132 E D Y G R Y K C E V 9 143 E G
L E D D T V V V 9 190 S F D Q L Y D A W R 9 261 F Y Y L I H P T K L
9 280 L N D G A Q I A K V 9 298 I L G Y D R C D A G 9 300 G Y D R C
D A G W L 9 333 R F V G F P D K K H 9 5 L L L V L I S I C W 8 15 A
D H L S D N Y T L 8 25 D H D R A I H I Q A 8 64 Y R D P T A F G S G
8 87 D Y L K E V D V F V 8 112 V F L K G G S D S D 8 122 A S L V I
T D L T L 8 160 V F P Y F P R L G R 8 183 D Q D A V I A S F D 8 189
A S F D Q L Y D A W 8 224 E P C G G Q N T V P 8 273 D E A V Q A C L
N D 8 287 A K V G Q I F A A W 8 302 D R C D A G W L A D 8 20 D N Y
T L D H D R A 7 62 K F Y R D P T A F G 7 69 A F G S G I H K I R 7
90 K E V D V F V S M G 7 107 G Y Q G R V F L K G 7 192 D Q L Y D A
W R G G 7 203 D W C N A G W L S D 7 226 C G G Q N T V P G V 7 250 V
F C F T S N F N G 7 251 F C F T S N F N G R 7 260 R F Y Y L I H P T
K 7 305 D A G W L A D G S V 7 311 D G S V R Y P I S R 7 338 P D K K
H K L Y G V 7 18 L S D N Y T L D H D 6 26 H D R A I H I Q A E 6 34
A E N G P H L L V E 6 36 N G P H L L V E A E 6 44 A E Q A K V F S H
R 6 49 V F S H R G G N V T 6 51 S H R G G N V T L P 6 66 D P T A F
G S G I H 6 102 K K T Y G G Y Q G R 6 118 S D S D A S L V I T 6 121
D A S L V I T D L T 6 133 D Y G R Y K C E V I 6 135 G R Y K C E V I
E G 6 211 S D G S V Q Y P I T 6 212 D G S V Q Y P I T K 6 213 G S V
Q Y P I T K P 6 247 R Y D V F C F T S N 6 259 G R F Y Y L I H P T 6
266 H P T K L T Y D E A 6 286 I A K V G Q I F A A 6 295 A W K I L G
Y D R C 6 303 R C D A G W L A D G 6 310 A D G S V R Y P I S 6 312 G
S V R Y P I S R P 6 326 S P T E A A V R F V 6 1 M K S L L L L V L I
5 12 I C W A D H L S D N 5 24 L D H D R A I H I Q 5 53 R G G N V T
L P C K 5 82 T K L T S D Y L K E 5 106 G G Y Q G R V F L K 5 108 Y
Q G R V F L K G G 5 131 L E D Y G R Y K C E 5 168 G R Y N L N F H E
A 5 204 W C N A G W L S D G 5 258 N G R F Y Y L I H P 5 283 G A Q I
A K V G Q I 5 293 F A A W K I L G Y D 5 2 K S L L L L V L I S 4 42
V E A E Q A K V F S 4 71 G S G I H K I R I K 4 92 V D V F V S M G Y
H 4 139 C E V I E G L E D D 4 157 Q G V V F P Y F P R 4 162 P Y F P
R L G R Y N 4 164 F P R L G R Y N L N 4 172 L N F H E A Q Q A C 4
188 I A S F D Q L Y D A 4 205 C N A G W L S D G g 4 215 V Q Y P I T
K P R E 4 222 P R E P C G G Q N T 4 232 V P G V R N Y G F W 4 245 K
S R Y D V F C F T 4 257 F N G R F Y Y L I H 4 304 C D A G W L A D G
S 4 314 V R Y P I S R P R R 4 316 Y P I S R P R R R C 4 342 H K L Y
G V Y C F R 4 28 R A I H I Q A E N G 3 30 I H I Q A E N G P H 3 65
R D P T A F G S G I 3 70 F G S G I H K I R I 3 72 S G I H K I R I K
W 3 77 I R I K W T K L T g 3 114 L K G G S D S D A g 3 198 W R G G
L D W C N A 3 200 G G L D W C N A G W 3 210 L 3 D G S V Q Y P I 3
221 K P R E P C G G Q N 3 225 P C G G Q N T V P G 3 238 Y G F W D K
D K S R 3 243 K D K S R Y D V F C 3 299 L G Y D R C D A G W 3 309 L
A D G S V R Y P I 3 318 I S R P R R R C S P 3 323 R R C S P T E A A
V 3 324 R C S P T E A A V R 3 332 V R F V G F P D K K 3 10 I S I C
W A D H L C 2 37 G P H L L V E A E Q 2 46 Q A K V F S H R G G 2 52
H R G G N V T L P C 2 60 P C K F Y R D P T A 2 63 F Y R D P T A F G
S 2 85 T S D Y L K E V D V 2 100 Y H K K T Y G G Y Q 2 101 H K K T
Y G G Y Q G 2 116 G G S D S D A S L V 2 117 G S D S D A S L V I 2
137 Y K C E V I E G L E 2 170 Y N L N F H E A Q Q 2 175 H E A Q Q A
C L D Q 2 178 Q Q A C L D Q D A V 2 180 A C L D Q D A V I A 2 197 A
W R G G L D W C N 2 216 Q Y P I T K P R E P 2 217 Y P I T K P R E P
C 2 220 T K P R E P C G G Q 2 228 G Q N T V P G V R N 2 236 R N Y G
F W D K D K 2 240 F W D K D K S R Y D 2 241 W D K D K S R Y D V 2
276 V Q A C L N D G A Q 2 277 Q A C L N D G A Q I 2 296 W K I L G Y
D R C D 2 315 R Y P I S R P R R R 2 319 S R P R R R C S P T 2 337 F
P D K K H K L Y G 2 340 K K H K L Y G V Y C 2 14 W A D H L S D N Y
T 1 21 N Y T L D H D R A I 1 38 P H L L V E A E Q A 1 47 A K V F S
H R G G N 1 59 L P C K F Y R D P T 1 74 I H K I R I K W T K 1 98 M
G Y H K K T Y G G 1 109 Q G R V F L K G G g 1 110 G R V F L K G G S
D 1 127 T D L T L E D Y G R 1 134 Y G R Y K C E V I E 1 138 K C E V
I E G L E D 1 167 L G R Y N L N F H E 1 169 R Y N L N F H E A Q 1
177 A Q Q A C L D Q D A 1 179 Q A C L D Q D A V I 1 184 Q D A V I A
S F D Q 1 191 F D Q L Y D A W R G 1 194 L Y D A W R G G L D 1 195 Y
D A W R G G L D W 1 199 R G G L D W C N A G 1 206 N A G W L S D G S
V 1 207 A G W L S D G S V Q 1 223 R E P C G G Q N T V 1 235 V R N Y
G F W D K D 1 237 N Y G F W D K D K C 1 246 S R Y D V F C F T S 1
265 I H P T K L T Y D E 1 268 T K L T Y D E A V Q 1 278 A C L N D G
A Q I A 1 289 V G Q I F A A W K I 1 294 A A W K I L G Y D R 1 306 A
G W L A D G S V R 1 320 R P R R R C S P T E 1 321 P R R R C S P T E
A 1 322 R R R C S P T E A A 1 345 Y G V Y C F R A Y N 1 151P3D4
v.2: HLA Peptide Scoring Results A26 10-mers SYFPEITHI 193 E I H Y
R K N K Q L 25 5 T T K T F P L R A L 24 298 P T S S S T Y D S L 24
45 G I I T Q G A K D F 22 369 D L A G S G Y C G A 22 20 S I R D H S
G Q K M 21 233 G F I F K T I A P L 21 56 H V Q F V G S Y K L 19 58
Q F V G S Y K L A Y 19 361 Y V E N G R P A D L 19 53 D F G H V Q F
V G S 18 106 S F C R N K L K Y L 18 204 R L Q K Q A E K N M 18 134
Q V P S R I F W R Q 17 172 E V G W K Y Q A V T 17 398 E R K A E N G
P H L 17 59 F V G S Y K L A Y S 16 79 D E K Q R K D K V L 16 108 C
R N K L K Y L A F 16 211 K N M K K K I D K Y 16 7 K T F P L R A L H
I 15 36 D L L V P T K V T G 15 37 L L V P T K V T G I 15 40 P T K V
T G I I T Q 15 54 F G H V Q F V G S Y 15 80 E K Q R K D K V L L 15
196 Y R K N K Q L M R L 15 244 A T R A T R I G H P 15 301 S S T Y D
S L S P Y 15 15 H I V V E S I R D H 14 42 K V T G I I T Q G A 14 50
G A K D F G H V Q F 14 95 V V S C E G I N I S 14 109 R N K L K Y L
A F L 14 111 K L K Y L A F L H K 14 187 K R K E K A E I H Y 14 190
E K A E I H Y R K N 14 234 F I F K T I A P L A 14 238 T I A P L A A
T R A 14 366 R P A D L A G S G Y 14 10 P L R A L H I V V E 13 16 I
V V E S I R D H S 13 23 D H S G Q K M K Q D 13 29 M K Q D K K V D L
L 13 47 I T Q G A K D F G H 13 68 S N D G E H W T V Y 13 75 T V Y Q
D E K Q R K 13 88 L L G R K A V V V S 13 102 N I S G S F C R N K 13
105 G S F C R N K L K Y 13 123 N T N P S R R P Y H 13 124 T N P S R
R P Y H F 13 131 Y H F Q V P S R I F 13 138 R I F W R Q E K A D 13
152 C P Q G H A S E A Y 13 182 A T L E E K R K E K 13 216 K I D K Y
T E S P G 13 237 K T I A P L A A T R 13 256 R T P R A G S S A H 13
275 P V P A A S P A A W 13 288 R T P W T R P S S C 13 291 W T R P S
S C P T g 13 295 S S C P T S S S T Y 13 352 K P K S E N N S W Y 13
377 G A L W K A I E S L 13 381 K A I E S L E E G L 13 384 E S L E E
G L G G K 13 4 H T T K T F P L R A 12 17 V V E S I R D H S G 12 32
D K K V D L L V P T 12 34 K V D L L V P T K V 12 94 V V V S C E G I
N I 12 163 K V C L S G A P H E 12 168 G A P H E V G W K Y 12 180 V
T A T L E E K R K 12 220 Y T E S P G G G S P 12 225 G G G S P R G L
G F 12 302 S T Y D S L S P Y G 12 342 N V L A R G K P Q R 12 356 E
N N S W Y V E N G 12 3 E H T T K T F P L R 11 8 T F P L R A L H I V
11 28 K M K Q D K K V D L 11 38 L V P T K V T G I I 11 43 V T G I I
T Q G A K 11 46 I I T Q G A K D F G 11 70 D G E H W T V Y Q D 11 74
W T V Y Q D E K Q R 11 86 K V L L G R K A V V 11 87 V L L G R K A V
V V 11 98 C E G I N I S G S F 11 179 A V T A T L E E K R 11 183 T L
E E K R K E K A 11 222 E S P G G G S P R G 11 223 S P G G G S P R G
L 11 227 G S P R G L G F I F 11 247 A T R I G H P G G R 11 306 S L
S P Y G P R N P 11 320 R H S P S G G G G L 11 343 V L A R G K P Q R
K 11 382 A I E S L E E G L G 11 385 S L E E G L G G K Q 11 389 G L
G G K Q K D K E 11 399 R K A E N G P H L L 11 64 K L A Y S N D G E
H 10 93 A V V V S C E G I N 10 100 G I N I S G S F C R 10 103 I S G
S F C R N K L 10 114 Y L A F L H K R M N 10 116 A F L H K R M N T N
10 117 F L H K R M N T N P 10 122 M N T N P S R R P Y 10 165 C L S
G A P H E V G 10 175 W K Y Q A V T A T L 10 201 Q L M R L Q K Q A E
10 241 P L A A T R A T R I 10 249 R I G H P G G R T P 10 261 G S S
A H R P P A L 10 276 V P A A S P A A W L 10 278 A A S P A A W L P L
10 315 P L P N P R H S P S 10 328 G L K K P A R H C Q 10 335 H C Q
G Q K H N V L 10 370 L A G S G Y C G A L 10 378 A L W K A I E S L E
10 13 A L H I V V E S I R 9 19 E S I R D H S G Q K 9 99 E G I N I S
G S F C 9 113 K Y L A F L H K R Y 9 147 D G G S C C P Q G H 9 157 A
S E A Y K K V C L 9 185 E E K R K E K A E I 9 194 I H Y R K N K Q L
M 9 269 A L S A R A P V P A 9 284 W L P L R T P W T R 9 305 D S L S
P Y G P R N 9 307 L S P Y G P R N P L 9 1 M L E H T T K T F P 8 2 L
E H T T K T F P L 8 97 S C E G I N I S G S 8 101 I N I S G S F C R
N 8 144 E K A D G G S C C P 8 159 E A Y K K V C L S G 8 160 A Y K K
V C L S G A 8 171 H E V G W K Y Q A V 8 207 K Q A E K N M K K K 8
231 G L G F I F K T I A 8 235 I F K T I A P L A A 8 264 A H R P P A
L S A R 8 286 P L R T P W T R P S 8 364 N G R P A D L A G S 8 387 E
E G L G G K Q K D 8 388 E G L G G K Q K D K 8 11 L R A L H I V V E
S 7 61 G S Y K L A Y S N D 7 72 E H W T V Y Q D E K 7 82 Q R K D K
V L L G R 7 83 R K D K V L L G R K 7 85 D K V L L G R K A V 7 89 L
G R K A V V V S C 7 127 S R R P Y H F Q V P 7 139 I F W R Q E K A D
G 7 155 G H A S E A Y K K V 7 167 S G A P H E V G W K 7 186 E K R K
E K A E I H 7 218 D K Y T E S P G G G 7 270 L S A R A P V P A A 7
310 Y G P R N P L P N P 7 323 P S G G G G L K K P 7 338 G Q K H N V
L A R G 7 363 E N G R P A D L A G 7 396 D K E R K A E N G P 7 31 Q
D K K V D L L V P 6 33 K K V D L L V P T K 6 51 A K D F G H V Q F V
6 57 V Q F V G S Y K L A 6 90 G R K A V V V S C E 6 129 R P Y H F Q
V P S R 6 132 H F Q V P S R I F W 6 133 F Q V P S R I F W R 6 174 G
W K Y Q A V T A T 6 199 N K Q L M R L Q K Q 6 210 E K N M K K K I D
K 6 214 K K K I D K Y T E S 6 226 G G S P R G L G F I 6 228 S P R G
L G F I F K 6 230 R G L G F I F K T I 6 236 F K T I A P L A A T 6
279 A S P A A W L P L R 6 337 Q G Q K H N V L A R 6 355 S E N N S W
Y V E N 6 380 W K A I E S L E E G 6 12 R A L H I V V E S I 5 41 T K
V T G I I T Q G 5 48 T Q G A K D F G H V 5 71 G E H W T V Y Q D E 5
81 K Q R K D K V L L G 5 112 L K Y L A F L H K R 5 158 S E A Y K K
V C L g 5 178 Q A V T A T L E E K 5 188 R K E K A E I H Y R 5 197 R
K N K Q L M R L Q 5 229 P R G L G F I F K T 5 248 T R I G H P G G R
T 5 251 G H P G G R T P R A 5 265 H R P P A L S A R A 5 272 A R A P
V P A A S P 5 281 P A A W L P L R T P 5 346 R G K P Q R K P K S 5
373 S G Y C G A L W K A 5 44 T G I I T Q G A K D 4 52 K D F G H V Q
F V G 4 115 L A F L H K R M N T 4 125 N P S R R P Y H F Q 4 146 A D
G G S C C P Q G 4 150 S C C P Q G H A S E 4 151 C C P Q G H A S E A
4 215 K K I D K
Y T E S P 4 255 G R T P R A G S S A 4 258 P R A G S S A H R P 4 274
A P V P A A S P A A 4 287 L R T P W T R P S S 4 304 Y D S L S P Y G
P R 4 312 P R N P L P N P R H 4 316 L P N P R H S P S G 4 325 G G G
G L K K P A R 4 329 L K K P A R H C Q G 4 350 Q R K P K S E N N g 4
360 W Y V E N G R P A D 4 394 Q K D K E R K A E N 4 395 K D K E R K
A E N G 4 14 L H I V V E S I R D 3 22 R D H S G Q K M K Q 3 69 N D
G E H W T V Y Q 3 77 Y Q D E K Q R K D K 3 96 V S C E G I N I S G 3
137 S R I F W R Q E K A 3 141 W R Q E K A D G G g 3 145 K A D G G S
C C P Q 3 192 A E I H Y R K N K Q 3 198 K N K Q L M R L Q K 3 205 L
Q K Q A E K N M K 3 217 I D K Y T E S P G G 3 219 K Y T E S P G G G
S 3 221 T E S P G G G S P R 3 232 L G F I F K T I A P 3 252 H P G G
R T P R A G 3 283 A W L P L R T P W T 3 292 T R P S S C P T S S 3
293 R P S S C P T S S S 3 303 T Y D S L S P Y G P 3 308 S P Y G P R
N P L P 3 314 N P L P N P R H S P 3 317 P N P R H S P S G G 3 322 S
P S G G G G L K K 3 330 K K P A R H C Q 3 Q 3 344 L A R G K P Q R K
P 3 347 G K P Q R K P K S E 3 351 R K P K S E N N S W 3 371 A G S G
Y C G A L W 3 374 G Y C G A L W K A I 3 386 L E E G L G G K Q K 3
391 G G K Q K D K E R K 3 393 K Q K D K E R K A E 3 18 V E S I R D
H S G Q 2 21 I R D H S G Q K M K 2 24 H S G Q K M K Q D K 2 25 S G
Q K M K Q D K K 2 26 G Q K M K Q D K K V 2 30 K Q D K K V D L L V 2
49 Q G A K D F G H V Q 2 55 G H V Q F V G S Y K 2 65 L A Y S N D G
E H W 2 76 V Y Q D E K Q R K D 2 78 Q D E K Q R K D K V 2 84 K D K
V L L G R K A 2 91 R K A V V V S C E G 2 119 H K R M N T N P S R 2
120 K R M N T N P S R R 2 128 R R P Y H F Q V P S 2 130 P Y H F Q V
P S R I 2 136 P S R I F W R Q E K 2 140 F W R Q E K A D G G 2 142 R
Q E K A D G G S C 2 143 Q E K A D G G S C C 2 156 H A S E A Y K K V
C 2 161 Y K K V C L S G A P 2 164 V C L S G A P H E V 2 166 L S G A
P H E V G W 2 169 A P H E V G W K Y Q 2 173 V G W K Y Q A V T A 2
177 Y Q A V T A T L E E 2 184 L E E K R K E K A E 2 189 K E K A E I
H Y R K 2 195 H Y R K N K Q L M R 2 202 L M R L Q K Q A E K 2 203 M
R L Q K Q A E K N 2 206 Q K Q A E K N M K K 2 208 Q A E K N M K K K
I 2 212 N M K K K I D K Y T 2 213 M K K K I D K Y T E 2 224 P G G G
S P R G L G 2 239 I A P L A A T R A T 2 246 R A T R I G H P G G 2
250 I G H P G G R T P R 2 252 P G G R T P R A G S 2 257 T P R A G S
S A H R 2 260 A G S S A H R P P A 2 262 S S A H R P P A L S 2 266 R
P P A L S A R A P 2 267 P P A L S A R A P V 2 268 P A L S A R A P V
P 2 271 S A R A P V P A A S 2 273 R A P V P A A S P A 2 277 P A A S
P A A W L P 2 280 S P A A W L P L R T 2 294 P S S C P T S S S T 2
299 T S S S T Y D S L S 2 309 P Y G P R N P L P N 2 313 R N P L P N
P R H S 2 319 P R H S P S G G G G 2 321 H S P S G G G G L K 2 324 S
G G G G L K K P A 2 326 G G G L K K P A R H 2 327 G G L K K P A R H
C 2 331 K P A R H C Q G Q K 2 332 P A R H C Q G Q K H 2 334 R H C Q
G Q K H N V 2 336 C Q G Q K H N V L A 2 348 K P Q R K P K S E N 2
349 P Q R K P K S E N N 2 353 P K S E N N S W Y V 2 362 V E N G R P
A D L A 2 365 G R P A D L A G S G 2 376 C G A L W K A I E g 2 379 L
W K A I E S L E E 2 390 L G G K Q K D K E R 2 392 G K Q K D K E R K
A 2 6 T K T F P L R A L H 1 27 Q K M K Q D K K V D 1 39 V P T K V T
G I I T 1 60 V G S Y K L A Y S N 1 62 S Y K L A Y S N D G 1 63 Y K
L A Y S N D G E 1 67 Y S N D G E H W T V 1 73 H W T V Y Q D E K Q 1
92 K A V V V S C E G I 1 110 N K L K Y L A F L H 1 118 L H K R M N
T N P g 1 121 R M N T N P S R R P 1 126 P S R R P Y H F Q V 1 135 V
P S R I F W R Q E 1 148 G G S C C P Q G H A 1 149 G S C C P Q G H A
C 1 153 P Q G H A S E A Y K 1 154 Q G H A S E A Y K K 1 162 K K V C
L S G A P H 1 170 P H E V G W K Y Q A 1 181 T A T L E E K R K E 1
191 K A E I H Y R K M K 1 200 K Q L M R L Q K Q A 1 209 A E K N M K
K K I D 1 240 A P L A A T R A T R 1 242 L A A T R A T R I G 1 243 A
A T R A T R I G H 1 245 T R A T R I G H P G 1 254 G G R T P R A G S
S 1 259 R A G S S A H R P P 1 263 S A H R P P A L S A 1 285 L P L R
T P W T R P 1 289 T P W T R P S S C P 1 296 S C P T S S S T Y D 1
297 C P T S S S T Y D S 1 300 S S S T Y D S L S P 1 318 N P R H S P
S G G G 1 333 A R H C Q G Q K H N 1 339 Q K H N V L A R G K 1 340 K
H N V L A R G K P 1 345 A R G K P Q R K P K 1 357 N N S W Y V E N G
R 1 358 N S W Y V E N G R P 1 367 P A D L A G S G Y C 1 375 Y C G A
L W K A I E 1 383 I E S L E E G L G G 1 397 K E R K A E N G P H
1
[0841]
48TABLE XLI SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4 v.1:
HLA Peptide Scoring Results B*0702 10-mers SYFPEITHI 59 L P C K F Y
R D P T 19 326 S P T E A A V R F V 18 266 H P T K L T Y D E A 17
105 Y G G Y Q G R V F L 15 145 L E D D T V V V A L 15 224 E P C G G
Q N T V P 15 122 A S L V I T D L T L 14 320 R P R R R C S P T E 14
337 F P D K K H K L Y G 14 115 K G G S D S D A S L 13 221 K P R E P
C G G Q N 13 9 L I S I C W A D H L 12 15 A D H L S D N Y T L 12 31
H I Q A E N G P H L 12 32 I Q A E N G P H L L 12 50 F S H R G G N V
T L 12 80 K W T K L T S D Y L 12 120 S D A S L V I T D L 12 147 D D
T V V V A L D L 12 158 G V V F P Y F P R L 12 164 F P R L G R Y N L
N 12 217 Y P I T K P R E P C 12 232 V P G V R N Y G F W 12 271 T Y
D E A V Q A C L 12 35 E N G P H L L V E A 11 37 G P H L L V E A E Q
11 66 D P T A F G S G I H 11 75 H K I R I K W T K L 11 136 R Y K C
E V I E 6 L 11 143 E G L E D D T V V V 11 163 Y F P R L G R Y N L
11 173 N F H E A Q Q A C L 11 185 D A V I A S F D Q L 11 193 Q L Y
D A W R G G L 11 201 G L D W C N A G W L 11 245 K S R Y D V F C F T
11 255 S N F N G R F Y Y L 11 261 F Y Y L I H P T K L 11 300 G Y D
R C D A G W L 11 309 L A D G S V R Y P I 11 316 Y P I S R P R R R C
11 322 R R R C S P T E A A 11 328 T E A A V R F V G F 11 335 V G F
P D K K H K L 11 1 M K S L L L L V L I 10 70 F G S G I H K I R I 10
76 K I R I K W T K L T 10 87 D Y L K E V D V F V 10 104 T Y G G Y Q
G R V F 10 117 G S D S D A S L V I 10 118 S D S D A S L V I T 10
142 I K G L E D D T V V 10 144 G L E D D T V V V A 10 155 D L Q G V
V F P Y F 10 161 F P Y F P R L G R Y 10 165 P R L G R Y N L N F 10
180 A C L D Q D A V I A 10 210 L S D G S V Q Y P I 10 280 L N D G A
Q I A K V 10 290 G Q I F A A W K X L 10 297 K I L G Y D R C D A 10
49 V F S H R G G N V T 9 85 T S D Y L K E V D V 9 89 L K E V D V F
V S M 9 103 K T Y G G Y Q G R V 9 121 D A S L V I T D L T 9 132 E D
Y G R Y K C E V 9 152 V A L D L Q G V V F 9 177 A Q Q A C L D Q D A
9 188 I A S F D Q L Y D A 9 198 W R G G L D W C N A 9 226 C G G Q N
T V P G V 9 242 D K D K S R Y D V F 9 244 D K S R Y D V F C F 9 269
K L T Y D E A V Q A 9 275 A V Q A C L N D G A 9 284 A Q I A K V G Q
I F 9 285 Q I A K V G Q I F A 9 321 P R R R C S P T E A 9 323 R R C
S P T E A A V 9 343 K L Y G V Y C F R A 9 33 Q A E N G P H L L V 8
41 L V E A E Q A K V F 8 61 C K F Y R D P T A F 8 68 T A F G S G I
H K I 8 86 S D Y L K E V D V F 8 95 F V S M G Y H K K T 8 113 F L K
G G S D S D A 8 116 G G S D S D A S L V 8 133 D Y G R Y K C E V I 8
141 V I E G L E D D T V 8 151 V V A L D L Q G V V 8 178 Q Q A C L D
Q D A V 8 179 Q A C L D Q D A V I 8 211 S D G S V Q Y P I T 8 231 T
V P G V R N Y G F 8 256 N F N G R F Y Y L I 8 278 A C L N D G A Q I
A 8 286 I A K V G Q I F A A 8 301 Y D R C D A G W L A 8 325 C S P T
E A A V R F 8 341 K H K L Y G V Y C F 8 14 W A D H L S D N Y T 7 21
H Y T L D H D R A I 7 23 T L D H D R A I H I 7 25 D H D R A I H I Q
A 7 34 A E N G P H L L V E 7 40 L L V E A E Q A K V 7 48 K V F S H
R G G N V 7 52 H R G G N V T L P C 7 60 P C K F Y R D P T A 7 65 R
D P T A F G S G I 7 73 G I H K I R I K W T 7 83 K L T S D Y L K E V
7 140 E V I E G L E D D T 7 150 V V V A L D L Q G V 7 153 A L D L Q
G V V F P 7 168 G R Y N L N F H E A 7 182 L D Q D A V I A S F 7 206
N A G W L S D G S V 7 222 P R E P C G G Q N T 7 223 R E P C G G Q N
T V 7 225 P C G G Q N T V P G 7 241 W D K D K S R Y D V 7 248 Y D V
F C F T S N F 7 259 G R F Y Y L I H P T 7 262 Y Y L I H P T K L T 7
267 P T K L T Y D E A V 7 277 Q A C L N D G A Q I 7 283 G A Q I A K
V G Q I 7 287 A K V G Q I F A A W 7 305 D A G W L A D G S V 7 319 S
R P R R R C S P T 7 338 P D K K H K L Y G V 7 3 S L L L L V L I S I
6 6 L L V L I S I C W A 6 20 D N Y T L D H D R A 6 38 P H L L V E A
E Q A 6 51 S H R G G N V T L P 6 54 G G N V T L P C K F 6 171 N L N
F H E A Q Q A 6 197 A W R G G L D W C N 6 252 C F T S N F N G R F 6
289 V G Q I F A A W K I 6 324 R C S P T E A A V R 6 331 A V R F V G
F P D K 6 17 H L S D N Y T L D H 5 107 G Y Q G R V F L K G 5 292 I
F A A W K I L G Y 5 318 I S R P R R R C S P 5 2 K S L L L L V L I g
4 26 H D R A I H I Q A E 4 42 V E A E Q A K V F S 4 44 A K Q A K V
F S H R 4 62 K F Y R D P T A F G 4 77 I R I K W T K L T S 4 114 L K
G G S D S D A C 4 134 Y G R Y K C E V I E 4 146 E D D T V V V A L D
4 243 K D K S R Y D V F C 4 247 R Y D V F C F T S N 4 303 R C D A G
W L A D G 4 310 A D G S V R Y P I g 4 329 E A A V R F V G F P 4 340
K K H K L Y G V Y C 4 45 E Q A K V F S H R G 3 47 A K V F S H R G G
N 3 53 R G G N V T L P C K 3 64 Y R D P T A F G S G 3 69 A F G S G
I H K I R 3 84 L T S D Y L K E V D 3 96 V S M G Y H K K T Y 3 119 D
S D A S L V I T D 3 124 L V I T D L T L E D 3 138 K C E V I E G L E
D 3 160 V F P Y F P R L G R 3 166 R L G R Y N L N F H 3 175 H E A Q
Q A C L D Q 3 181 C L D Q D A V I A S 3 183 D Q D A V I A S F D 3
186 A V I A S F D Q L Y 3 187 V I A S F D Q L Y D 3 189 A S F D Q L
Y D A W 3 195 Y D A W R G G L D W 3 199 R G G L D W C N A G 3 205 C
N A G W L S D G S 3 207 A G W L S D G S V Q 3 209 W L S D G S V Q Y
P 3 234 G V R N Y G F W D K 3 236 R N Y G F W D K D K 3 253 F T S N
F N G R F Y 3 257 F N G R F Y Y L I H 3 273 D E A V Q A C L N D 3
281 N D G A Q I A K V G 3 282 D G A Q I A K V G Q 3 288 K V G Q I F
A A W K 3 294 A A W K I L G Y D R 3 298 I L G Y D R C D A G 3 302 D
R C D A G W L A D 3 304 C D A G W L A D G S 3 306 A G W L A D G S V
R 3 307 G W L A D G S V R Y 3 313 S V R Y P I S R P R 3 314 V R Y P
I S R P R R 3 317 P I S R P R R R C S 3 327 P T E A A V R F V G 3
330 A A V R F V G F P D 3 333 R F V G F P D K K H 3 344 L Y G V Y C
F R A Y 3 11 S I C W A D H L S D 2 12 I C W A D H L S D N 2 22 Y T
L D H D R A I H 2 27 D R A I H I Q A E N 2 29 A I H I Q A E N G P 2
30 I H I Q A E N G P H 2 36 N G P H L L V E A E 2 43 E A E Q A K V
F S H 2 57 V T L P C K F Y R D 2 63 F Y R D P T A F G S 2 78 R I K
W T K L T S D 2 79 I K W T K L T S D Y 2 82 T K L T S D Y L K E 2
88 Y L K E V D V F V S 2 90 K E V D V F V S M G 2 91 E V D V F V S
M G Y 2 97 S M G Y H K K T Y G 2 109 Q G R V F L K G G S 2 126 I T
D L T L E D Y G 2 135 G R Y K C E V I E G 2 149 T V V V A L D L Q G
2 154 L D L Q G V V F P Y 2 156 L Q G V V F P Y F P 2 167 L G R Y N
L N F H E 2 169 R Y N L N F H E A Q 2 190 S F D Q L Y D A W R 2 194
L Y D A W R G G L D 2 203 D W C N A G W L S D 2 208 G W L S D G S V
Q Y 2 212 D G S V Q Y p I T K 2 214 S V Q Y P I T K P R 2 215 V Q Y
P I T K P R E 2 218 P I T K P R E P C G 2 219 I T K P R E P C G G 2
228 G Q N T V P G V R N 2 230 N T V P G V R N Y G 2 240 F W D K D K
S R Y D 2 258 N G R F Y Y L I H P 2 260 R F Y Y L I H P T K 2 263 Y
L I H P T K L T Y 2 264 L I H P T K L T Y D 2 265 I H P T K L T Y D
E 2 268 T K L T Y D E A V Q 2 270 L T Y D E A V Q A C 2 276 V Q A C
L N D G A Q 2 295 A W K I L G Y D R C 2 308 W L A D G S V R Y P 2
311 D G S V R Y P I S R 2 345 Y G V Y C F R A Y N 2 7 L V L I S I C
W A D 1 8 V L I S I C W A D H 1 10 I S I C W A D H L S 1 13 C W A D
H L S D N Y 1 16 D H L S D N Y T L D 1 18 L S D N Y T L D H D 1 28
R A I H I Q A E N G 1 39 H L L V E A E Q A K 1 55 G N V T L P C K F
Y 1 67 P T A F G S G I H K 1 71 G S G I H K I R I K 1 72 S G I H K
I R I K W 1 74 I H K I R I K W T K 1 98 M G Y H K K T Y G G 1 99 G
Y H K K T Y G G Y 1 100 Y H K K T Y G G Y Q 1 102 K K T Y G G Y Q G
R 1 106 G G Y Q G R V F L K 1 108 Y Q G R V F L K G G 1 111 R V F L
K G G S D S 1 112 V F L K G G S D S D 1 123 S L V I T D L T L E 1
130 T L E D Y G R Y K C 1 131 L E D Y G R Y K C E 1 157 Q G V V F P
Y F P R 1 159 V V F P Y F P R L G 1 162 P Y F P R L G R Y N 1 170 Y
N L N F H E A Q Q 1 172 L N F H E A Q Q A C 1 174 F H E A Q Q A C L
D 1 176 E A Q Q A C L D Q D 1 184 Q D A V I A S F D Q 1 200 G G L D
W C N A G W 1 204 W C N A G W L S D G 1 213 G S V Q Y P I T K P 1
227 G G Q N T V P G V R 1 229 Q N T V P G V R N Y 1 237 N Y G F W D
K D K S 1 249 D V F C F T S N F N 1 251 F C F T S N F N G R 1 254 T
S N F N G R F Y Y 1 272 Y D E A V Q A C L N 1 274 E A V Q A C L N D
G 1 279 C L N D G A Q I A K 1 291 Q I F A A W K I L G 1 293 F A A W
K I L G Y D 1 299 L G Y D R C D A G W 1 315 R Y P I S R P R R R 1
334 F V G F P D K K H K 1 339 D K K H K L Y G V Y 1 342 H X L Y G V
Y C F R 1 v.2: HLA Peptide Scoring Results B*0702 10-mers SYFPEITHI
223 S P G G G S P R G L 23 276 V P A A S P A A W L 23 274 A P V P A
A S P A A 21 267 P P A L S A R A P V 20 280 S P A A W L P L R T 20
278 A A S P A A W L P L 18 9 F P L R A L H I V V 17 39 V P T K V T
G I I T 17 228 S P R G L G F I F K 16 322 S P S G G G G L K K 16
157 A S E A Y K K V C L 15 240 A P L A A T R A T R 15 261 G S S A H
R P P A L 15 252 H P G G R T P R A G 14 257 T P R A G S S A H R 14
269 A L S A R A P V P A 14 293 R P S S C P T S S S 14 320 R H S P S
G G G G L 14 28 K M K Q D K K V D L 13 80 E K Q R K D K V L L 13
103 I S G S F C R N K L 13 109 R N K L K Y L A F L 13 125 N P S R R
P Y H F Q 13 129 R P Y H F Q V P S R 13 152 C P Q G H A S E A Y 13
260 A G S S A H R P P A 13 266 R P P A L S A R A P 13 308 S P Y G P
R N P L P 13 311 G P R N P L P N P R 13 335 H C Q G Q K H N V L 13
398 E R K A E N G P H L 13 2 L E H T T K T F P L 12 135 V P S R I F
W R Q E 12 169 A P H E V G W K Y Q 12 175 W K Y Q A V T A T L 12
233 G F I F K T I A P L 12 298 P T S S S T Y D S L 12 307 L S P Y G
P R N P L 12 314 N P L P N P R H S P 12 316 L P N P R H S P S G 12
318 N P R H S P S G G G 12 331 K P A R H C Q G Q K 12 366 R P A D L
A G S G Y 12 370 L A G S G Y C G A L 12 399 R K A E N G P H L L 12
5 T T K T F P L R A L 11 29 M K Q D K K V D L L 11 30 K Q D K K V D
L L V 11 51 A K D F G H V Q F V 11 79 D E K Q R K D K V L 11 87 V L
L G R K A V V V 11 193 E I H Y R K N K Q L 11 283 A W L P L R T P W
T 11 285 L P L R T P W T R P 11 297 C P T S S S T Y D S 11 348 K P
Q R K P K S E N 11 352 K P K S E N N S W Y 11 361 Y V E N G R P A D
L 11 381 K A I E S L E E G L 11 7 K T F P L R A L H I 10 42 K V T G
I I T Q G A 10 56 H V Q F V G S Y K L 10 66 A Y S N D G E H W T 10
106 3 F C R N K L K Y L 10 108 C R N K L K Y L A F 10 172 E V G W K
Y Q A V T 10 196 Y R K N K Q L M R L 10 226 G G S P R G L G F I 10
230 R G L G F I F K T I 10 235 I F K T I A P L A A 10 251 G H P G G
R T P R A 10 270 L S A R A P V P A A 10 289 T P W T R P S S C P 10
324 S G G G G L K K P A 10 377 G A L W K A I E S L 10 4 H T T K T F
P L R A 9 32 D K K V D L L V P T 9 34 K V D L L V P T K V 9 37 L L
V P T K V T G I 9 48 T Q G A K D F G H V 9 86 K V L L G R K A V V 9
160 A Y K K V C L S G A 9 171 H E V G W K Y Q A V 9 173 V G W K Y Q
A V T A 9 174 G W K Y Q A V T A T 9 225 G G G S P R G L G F 9 238 T
I A P L A A T R A 9 239 I A P L A A T R A T 9 241 P L A A T R A T R
I 9 336 C Q G Q K H N V L A 9 369 D L A G S G Y C G A 9 374 G Y C G
A L W K A I 9 12 R A L H I V V E S I 8 20 S I R D H S G Q K M 8 35
V D L L V P T K V T 8 50 G A K D F G H V Q F 8 85 D K V L L G R K A
V 8 107 F C R N K L K Y L A 8 113 K Y L A F L H K R M 8 126 P S R R
P Y H F Q V 8 148 G G S C C P Q G H A 8 185 E E K R K E K A E I 8
204 R L Q K Q A E K N M 8 231 G L G F I F K T I A 8 234 F I F K T I
A P L A 8 236 F K T I A P L A A T 8 248 T R I G H P G G R T 8 263 S
A H R P P A L S A 8 265 H R P P A L S A R A 8 273 R A P V P A A S P
A 8 294 P S S C P T S S S T 8 353 P K S E N N S W Y V 8 362 V E N G
R P A D L A 8 38 L V P T K V T G I I 7 78 Q D E K Q R K D K V 7 81
K Q R K D K V L L G 7 84 K D K V L L G R K A 7 92 K A V V V S C E G
I 7 98 C E G I N I S G S F 7 115 L A F L H K R M N T 7 155 G H A S
E A Y K K V 7 194 I H Y R K N K Q L M 7 200 K Q L M R L Q K Q A 7
208 Q A E K N M K K K I 7 212 N M K K K I D K Y T 7 229 P R G L G F
I F K T 7 255 G R T P R A G S S A 7 290 P W T R P S S C P T 7 334 R
H C Q G Q K H N V 7 359 S W Y V E N G R P A 7 371 A G S G Y C G A L
W 7 392 G K Q K D K E R K A 7 8 T F P L R A L H I V 6 10 P L R A L
H I V V E 6 26 G Q K M K Q D K K V 6 45 G I I T Q G A K D F 6 57 V
Q F V G S Y K L A 6 67 Y S N D G E H W T V 6 89 L 6 R K A V V V S C
6 94 V V V S C E G I N I 6 124 T N P S R R P Y H F 6 130 P Y H F Q
V P S R I 6 131 Y H F Q V P S R I F 6 137 S R I F W R Q E K A 6 146
A D G G S C C P Q G 6 151 C C P Q G H A S E A 6 164 V C L S G A P H
E V 6 170 P H E V G W K Y Q A 6 183 T L E E K R K E K A 6 227 G S P
R G L G F I F 6 264 A H R P P A L S A R 6 345 A R G K P Q R K P K 6
373 S G Y C G A L W K A 6 58 Q P V G S Y K L A Y 5 68 S H D G E H W
T V Y 5 88 L L G R K A V V V S 5 127 S R R P Y H F Q V P 5 145 K A
D G G S C C P Q 5 165 C L S G A P H E V G 5 195 H Y R K N K Q L M R
5 244 A T R A T R I G H P 5 250 I 6 H P G G R T P R 5 271 S A R A P
V P A A S 5 272 A R A P V P A A S P 5 282 A A W L P L R T P W 5 309
P Y G P R N P L P N 5 325 G 6 G G L K K P A R 5 337 Q 6 Q K H N V L
A R 5 363 E N G R P A D L A G 5 383 I E S L E E G L 6 G 5 397 K E R
K A E N G P H 5 11 L R A L H I V V E C 4 23 D H S G Q K M K Q D 4
31 Q D K K V D L L V P 4 52 K D F G H V Q F V G 4 53 D F G H V Q F
V G C 4 69 N D G E H W T V Y Q 4 102 N I S G S F C R N K 4 111 K L
K Y L A F L H K 4 128 R R P Y H F Q V P C 4 159 E A Y K K V C L S G
4 166 L S G A P H E V G W 4 177 Y Q A V T A T L E E 4 186 E K R K E
K A E I H 4 198 K N K Q L M R L Q K 4 216 K I D K Y T E S P G 4 221
T E S P G G G S P R 4 222 E S P G G G S P R G 4 224 P G G G S P R G
L G 4 247 A T R I G H P G G R 4 279 A S P A A W L P L R 4 286 P L R
T P W T R P S 4 291 W T R P S S C P T S 4 300 S S S T Y D S L S P 4
344 L A R G K P Q R K P 4 364 N G R P A D L A G S 4 3 E H T T K T F
P L R 3 27 Q K M K Q D K K V D 3 33 K K V D L L V P T K 3 47 I T Q
G A K D F G H 3 49 Q G A K D F G H V Q 3 83 R K D K V L L G R K 3
119 H K R M N T N P S R 3 123 N T N P S R R P Y H 3 136 P S R I F W
R Q E K 3 156 H A S E A Y K K V C 3 162 K K V C L S G A P H 3 167 S
G A P H E V G W K 3 176 K Y Q A V T A T L E 3 179 A V T A T L E E K
R 3 182 A T L E E K R K E K 3 202 L M R L Q K Q A E K 3 211 K N M K
K K I D K Y 3 237 K T I A P L A A T R 3 243 A A T R A T R I G H 3
253 P G G R T P R A G S 3 258 P R A G S S A H R P 3 259 R A G S S A
H R P P 3 275 P V P A A S P A A W 3 287 L R T P W T R P S S 3 304 Y
D S L S P Y G P R 3 306 S L S P Y G P R N P 3 323 P S G G G G L K K
P 3 346 R G K P Q R K P K S 3 349 P Q R K P K S E N N 3 360 W Y V E
N G R P A D 3 368 A D L A G S G Y C G 3 372 G S G Y C G A L W K 3
375 Y C G A L W K A I E 3 378 A L W K A I E S L E 3 379 L W K A I E
S L E E 3 388 E G L G G K Q K D K 3 389 G L G G K Q K D K E 3 393 K
Q K D K E R K A E 3 394 Q K D K E R K A E N 3 1 M L E H T T K T F P
2 6 T K T F P L R A L H 2 13 A L H I V V E S I R 2 16 I V V E S I R
D H S 2 18 V K S I R D H S G Q 2 21 I R D H S G Q K M K 2 36 D L L
V P T K V T G 2 43 V T G I I T Q G A K 2 46 I I T Q G A K D
F G 2 59 F V G S Y K L A Y S 2 60 V G S Y K L A Y S N 2 64 K L A Y
S N D G E H 2 77 Y Q D E K Q R K D K 2 82 Q R K D K V L L G R 2 90
G R K A V V V S C E 2 91 R K A V V V S C E G 2 93 A V V V S C E G I
N 2 95 V V S C E G I N I S 2 97 S C E G I N I S G C 2 99 E G I N I
S G S F C 2 101 I N I S G S F C R N 2 104 S G S F C R N K L K 2 105
G S F C R N K L K Y 2 116 A F L H K R M N T N 2 117 F L H K R M N T
N P 2 118 L H K R M N T N P S 2 120 K R M N T N P S R R 2 122 M N T
N P S R R P Y 2 132 H F Q V P S R I F W 2 138 R I F W R Q E K A D 2
139 I F W R Q E K A D G 2 140 F W R Q E K A D G G 2 142 R Q E K A D
G G S C 2 144 E K A D G G S C C P 2 150 S C C P Q G H A S E 2 153 P
Q G H A S E A Y K 2 158 S K A Y K K V C L S 2 163 K V C L S G A P H
E 2 184 L E E K R K E K A E 2 188 R K E K A E I H Y R 2 189 K E K A
E I H Y R K 2 190 E K A E I H Y R K N 2 191 K A E I H Y R K N K 2
192 A E I H Y R K N K Q 2 197 R K N K Q L M R L Q 2 201 Q L M R L Q
K Q A E 2 207 K Q A E K N M K K K 2 209 A E K N M K K K I D 2 214 K
K K I D K Y T E C 2 215 K K I D K Y T E S P 2 217 I D K Y T E S P G
G 2 232 L G F I F K T I A P 2 242 L A A T R A T R I G 2 245 T R A T
R I G H P G 2 246 R A T R I G H P G G 2 249 R I G H P G G R T P 2
254 G G R T P R A G S S 2 256 R T P R A G S S A H 2 262 S S A H R P
P A L S 2 268 P A L S A R A P V P 2 299 T S S S T Y D S L S 2 312 P
R N P L P N P R H 2 326 G G G L K K P A R H 2 328 G L K K P A R H C
Q 2 330 K K P A R H C Q G Q 2 332 P A R H C Q G Q K H 2 333 A R H C
Q G Q K H N 2 340 K H N V L A R G K P 2 342 N V L A R G K P Q R 2
351 R K P K S E N N S W 2 354 K S E N N S W Y V E 2 355 S E N N S W
Y V E N 2 356 E N N S W Y V E N G 2 357 N N S W Y V E N G R 2 382 A
I E S L E E G L G 2 386 L E E G L G G K Q K 2 387 E E G L G G K Q K
D 2 390 L G G K Q K D K E R 2 19 E S I R D H S G Q K 1 22 R D H S G
Q K M K Q 1 24 H S G Q K M K Q D K 1 25 S G Q K M K Q D K K 1 41 T
K V T G I I T Q G 1 44 T G I I T Q G A K D 1 54 F G H V Q F V G S Y
1 61 G S Y K L A Y S N D 1 63 Y K L A Y S N D G E 1 70 D G E H W T
V Y Q D 1 72 E H W T V Y Q D E K 1 110 W K L K Y L A F L H 1 114 Y
L A F L H K R M N 1 121 R M N T N P S R R P 1 133 F Q V P S R I F W
R 1 134 Q V P S R I F W R Q 1 143 Q E K A D G G S C C 1 147 D G G S
C C P Q G H 1 149 G S C C P Q G H A S 1 154 Q G H A S E A Y K K 1
161 Y K K V C L S G A P 1 180 V T A T L E E K R K 1 187 K R K E K A
E I H Y 1 206 Q K Q A E K N M K K 1 210 E K N M K K K I D K 1 213 M
K K K I D K Y T E 1 219 K Y T E S P G G G C 1 277 P A A S P A A W L
P 1 281 P A A W L P L R T P 1 288 R T P W T R P S S C 1 292 T R P s
S C P T S S 1 295 S S C P T S S S T Y 1 296 S C P T S S S T Y D 1
301 S S T Y D S L S P Y 1 302 S T Y D S L S P Y G 1 303 T Y D S L S
P Y G P 1 305 D S L S P Y G P R N 1 310 Y G P R N P L P N P 1 313 R
N P L P N P R H S 1 315 P L P N P R H S P S 1 327 G G L K K P A R H
C 1 329 L K K P A R H C Q G 1 338 G Q K H N V L A R G 1 341 H N V L
A R G K P Q 1 343 V L A R G K P Q R K 1 350 Q R K P K S E N N S 1
365 G R P A D L A G S G 1 367 P A D L A G S G Y C 1 376 C G A L W K
A I E S 1 380 W K A I E S L E E G 1 384 E S L E E G L G G K 1 395 K
D K E R K A E N G 1
[0842]
49TABLE XLII SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4: HLA
Peptide Scoring Results B*08 10-mers SYFPEITHI NO DATA
[0843]
50TABLE XLIII SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4:
HLA Peptide Scoring Results B*1510 10-mers SYFPEITHI NO DATA
[0844]
51TABLE XLIV SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4: HLA
Peptide Scoring Results B*2705 10-mers SYFPEITHI NO DATA
[0845]
52TABLE XLV SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4: HLA
Peptide Scoring Results B*2709 10-mers SYFPEITHI NO DATA
[0846]
53TABLE XLVI SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4 v.1:
HLA Peptide Scoring Results B*4402 10-mers SYFPEITHI 145 L K D D T
V V V A L 26 328 T E A A V R F V G F 22 189 A S F D Q L Y D A W 18
34 A E N G P H L L V E 17 72 S G I H K I R I K W 17 186 A V I A S F
D Q L Y 17 287 A K V G Q I F A A W 17 335 V G F P D K K H K L 17 68
T A F G S G I H K I 16 122 A S L V I T D L T L 16 284 A Q I A K V G
Q I F 16 15 A D H L S D N Y T L 15 61 C K F Y R D P T A F 15 75 H K
I R I K W T K L 15 96 V S M G Y H K K T Y 15 255 S N F N G R F Y Y
L 15 263 Y L I H P T K L T Y 15 290 G Q I F A A W K I L 15 336 G F
P D K K H K L Y 15 41 L V E A E Q A K V F 14 44 A E Q A K V F S H R
14 86 S D Y L K E V D V F 14 120 S D A S L V I T D L 14 152 V A L D
L Q G V V F 14 182 L D Q D A V I A S F 14 292 I F A A W K I L G Y
14 325 C S P T E A A V R F 14 344 L Y G V Y C F R A Y 14 1 M K S L
L L L V L I 13 3 S L L L L V L I S I 13 21 N Y T L D H D R A I 13
32 I Q A E N G P H L L 13 50 F S H R G G N V T L 13 55 G N V T L P
C K F Y 13 90 K E V D V F V S M G 13 91 E V D V F V S M G Y 13 104
T Y G G Y Q G R V F 13 131 L E D Y G R Y K C E 13 136 R Y K C E V I
E G L 13 163 Y F P R L G R Y N L 13 165 P R L G R Y N L N F 13 208
G W L S D G S V Q Y 13 223 R E P C G G Q N T V 13 244 D K S R Y D V
F C F 13 253 F T S N F N G R F Y 13 261 F Y Y L I H P T K L 13 300
G Y D R C D A G W L 13 341 K H K L Y G V Y C F 13 3 L L L V L I S I
C W 12 9 L I S I C W A D H L 12 54 G G N V T L P C K F 12 79 I K W
T K L T S D Y 12 105 Y G G Y Q G R V F L 12 125 V I T D L T L E D Y
12 142 I E G L E D D T V V 12 147 D D T V V V A L D L 12 154 L D L
Q G V V F P Y 12 155 D L Q G V V F P Y F 12 185 D A V I A S F D Q L
12 193 Q L Y D A W R G G L 12 200 G G L D W C N A G W 12 201 G L D
W C N A G W L 12 229 Q N T V P G V R N Y 12 231 T V P G V R N Y G F
12 242 D K D K S R Y D V F 12 307 G W L A D G S V R Y 12 13 C W A D
H L S D N Y 11 23 T L D H D R A I H I 11 42 V H A E Q A K V F S 11
70 F G S G I H K I R I 11 80 K W T K L T S D Y L 11 115 K G G S D S
D A S L 11 117 G S D S D A S L V I 11 128 D L T L E D Y G R Y 11
139 C E V I E G L E D D 11 158 G V V F P Y F P R L 11 161 F P Y F P
R L G R Y 11 173 N F H E A Q Q A C L 11 175 H E A Q Q A C L D Q 11
195 Y D A W R G G L D W 11 239 G F W D K D K S R Y 11 248 Y D V F C
F T S N F 11 254 T S N F N G R F Y Y 11 256 N F N G R F Y Y L I 11
271 T Y D E A V Q A C L 11 273 D E A V Q A C L N D 11 299 L G Y D R
C D A G W 11 309 L A D G S V R Y P I 11 339 D K K H K L Y G V Y 11
31 H I Q A E N G P H L 10 65 R D P T A F G S G I 10 99 G y H K K T
Y G G Y 10 133 D Y G R Y K C E V I 10 179 Q A C L D Q D A V I 10
210 L S D G S V Q Y P I 10 232 V P G V R N Y G F W 10 252 C F T S N
F N G R F 10 277 Q A C L N D G A Q I 10 283 G A Q I A K V G Q I 10
289 V G Q I F A A W K I 10 159 V V F P Y F P R L G 8 35 E N G P H L
L V E A 7 153 A L D L Q G V V F P 7 180 A C L D Q D A V I A 7 124 L
V I T D L T L E D 6 143 E G L E D D T V V V 6 146 E D D T V V V A L
D 6 162 P y F P R L G R Y N 6 230 N T V P G V R N Y G 6 259 G R F Y
Y L I H P T 6 278 A C L N D G A Q I A 6 280 L N D G A Q I A K V 6
324 R C S P T E A A V R 6 2 K S L L L L V L I S 5 4 L L L L V L I S
I C 5 10 I S I C W A D H L S 5 24 L D H D R A I H I Q 5 26 H D R A
I H I Q A E 5 36 N G P H L L V E A E 5 57 V T L P C K F Y R D 5 64
Y R D P T A F G S G 5 69 A F G S G I H K I R 5 73 G I H K I R I K W
T 5 76 K I R I K W T K L T 5 77 I R I K W T K L T S 5 118 S D S D A
S L V I T 5 140 E V I E G L E D D T 5 181 C L D Q D A V I A S 5 207
A G W L S D G S V Q 5 217 Y P I T K P R E P C 5 251 F C F T S N F N
G R 5 262 Y Y L I H P T K L T 5 281 N D G A Q I A K V G 5 286 I A K
V G Q I F A A 5 296 W K I L G Y D R C D 5 306 A G W L A D G S V R 5
316 Y P I S R P R R R C 5 6 L L V L I S I C W A 4 17 H L S D N Y T
L D H 4 25 D H D R A I H I Q A 4 28 R A I H I Q A E N G 4 29 A I H
I Q A E N G P 4 38 P H L L V E A E Q A 4 47 A K V F S H R G G N 4
51 S H R G G N V T L P 4 71 G S G I H K I R I K 4 82 T K L T S D Y
L K E 4 83 K L T S D Y L K E V 4 95 F V S M G Y H K K T 4 107 G Y Q
G R V F L K G 4 108 Y Q G R V F L K G G 4 116 G G S D S D A S L V 4
119 D S D A S L V I T D 4 121 D A S L V I T D L T 4 144 G L E D D T
V V V A 4 172 L N F H E A Q Q A C 4 176 E A Q Q A C L D Q D 4 197 A
W R G G L D W C N 4 199 R G G L D W C N A G 4 212 D G S V Q Y P I T
K 4 213 G S V Q Y P I T K P 4 214 S V Q Y P I T K P R 4 219 I T K P
R E P C G G 4 224 E P C G G Q N T V P 4 238 Y G F W D K D K S R 4
264 L X H P T K L T Y D 4 269 K L T Y D E A V Q A 4 270 L T Y D E A
V Q A C 4 274 E A V Q A C L N D G 4 279 C L N D G A Q I A K 4 291 Q
I F A A W K I L G 4 297 K I L G Y D R C D A 4 302 D R C D A G W L A
D 4 312 G S V R Y P I S R P 4 314 V R Y P I S R P R R 4 317 P I S R
P R R R C S 4 318 I S R P R R R C S P 4 330 A A V R F V G F P D 4
331 A V R F V G F P D K 4 332 V R F V G F P D K K 4 333 R F V G F P
D K K H 4 7 L V L I S I C W A D 3 8 V L I S I C W A D H 3 18 L S D
N Y T L D H D 3 22 Y T L D H D R A I H 3 30 I H I Q A E N G P H 3
33 Q A E N G P H L L V 3 39 H L L V E A E Q A K 3 43 E A E Q A K V
F S H 3 45 E Q A K V F S H R G 3 48 K V F S H R G G N V 3 49 V F S
H R G G N V T 3 52 H R G G N V T L P C 3 62 K F Y R D P T A F G 3
84 L T S D Y L K E V D 3 111 R V F L K G G S D S 3 114 L K G G S D
S D A Q 3 123 S L V I T D L T L E 3 130 T L E D Y G R Y K C 3 132 E
D Y G R Y K C E V 3 160 V F P Y F P R L G R 3 164 F P R L G R Y N L
N 3 166 R L G R Y N L N F H 3 168 G R Y N L N F H E A 3 169 R Y N L
N F H E A Q 3 170 Y N L N F H E A Q Q 3 171 N L N F H E A Q Q A 3
177 A Q Q A C L D Q D A 3 209 W L S D G S V Q Y P 3 215 V Q Y P I T
K P R E 3 216 Q Y P I T K P R E P 3 222 P R E P C G G Q N T 3 225 P
C G G Q N T V P G 3 227 G G Q N T V P G V R 3 236 R N Y G F W D K D
K 3 246 S R Y D V F C F T S 3 249 D V F C F T S N F N 3 258 N G R F
Y Y L I H P 3 265 I H P T K L T Y D E 3 267 P T K L T Y D E A V 3
268 T K L T Y D E A V Q 3 275 A V Q A C L N D G A 3 294 A A W K I L
G Y D R 3 295 A W K I L G Y D R C 3 308 W L A D G S V R Y P 3 310 A
D G S V R Y P I S 3 311 D G S V R Y P I S R 3 315 R Y P I S R P R R
R 3 319 S R P R R R C S P T 3 322 R R R C S P T E A A 3 326 S P T E
A A V R F V 3 329 E A A V R F V G F P 3 11 S I C W A D H L S D 2 14
W A D H L S D N Y T 2 16 D H L S D N Y T L D 2 19 S D N Y T L D H D
R 2 53 R G G N V T L P C K 2 56 N V T L P C K F Y R 2 58 T L P C K
F Y R D P 2 63 F Y R D P T A F G S 2 81 W T K L T S D Y L K 2 85 T
S D Y L K E V D V 2 87 D Y L K E V D V F V 2 88 Y L K E V D V F V S
2 89 L K E V D V F V S M 2 93 D V F V S M G Y H K 2 94 V F V S M G
Y H K K 2 101 H K K T Y G G Y Q G 2 103 K T Y G G Y Q G R V 2 106 G
G Y Q G R V F L K 2 126 I T D L T L E D Y G 2 127 T D L T L E D Y G
R 2 129 L T L E D Y G R Y K 2 135 G R Y K C E V I E G 2 138 K C E V
I E G L E D 2 141 V I E G L E D D T V 2 148 D T V V V A L D L Q 2
149 T V V V A L D L Q G 2 151 V V A L D L Q G V V 2 174 F H E A Q Q
A C L D 2 178 Q Q A C L D Q D A V 2 183 D Q D A V I A S F D 2 188 I
A S F D Q L Y D A 2 190 S F D Q L Y D A W R 2 191 F D Q L Y D A W R
G 2 192 D Q L Y D A W R G G 2 194 L Y D A W R G G L D 2 196 D A W R
G G L D W C 2 203 D W C N A G W L S D 2 220 T K P R E P C G G Q 2
221 K P R E P C G G Q N 2 228 G Q N T V P G V R N 2 234 G V R N Y G
F W D K 2 237 N Y G F W D K D K S 2 240 F W D K D K S R Y D 2 241 W
D K D K S R Y D V 2 243 K D K S R Y D V F C 2 245 K S R Y D V F C F
T 2 247 R Y D V F C F T S N 2 257 F N G R F Y Y L I H 2 272 Y D E A
V Q A C L N 2 276 V Q A C L N D G A Q 2 288 K V G Q I F A A W K 2
298 I L G Y D R C D A G 2 303 R C D A G W L A D G 2 304 C D A G W L
A D G S 2 313 S V R Y P I S R P R 2 320 R P R R R C S P T E 2 321 P
R R R C S P T K A 2 323 R R C S P T E A A V 2 327 P T E A A V R F V
G 2 334 F V G F P D K K H K 2 337 F P D K K H K L Y G 2 340 K K H K
L Y G V Y C 2 343 K L Y G V Y C F R A 2 12 I C W A D H L S D N 1 20
D N Y T L D H D R A 1 37 G P H L L V E A E Q 1 40 L L V E A E Q A K
V 1 46 Q A K V F S H R G G 1 59 L P C K F Y R D P T 1 60 P C K F Y
R D P T A 1 67 P T A F G S G I H K 1 74 I H K I R I K W T K 1 78 R
I K W T K L T S D 1 97 S M G Y H K K T Y G 1 98 M G Y H K K T Y G G
1 102 K K T Y G G Y Q G R 1 112 V F L K G G S D S D 1 113 F L K G G
S D S D A 1 134 Y G R Y K C E V I E 1 137 Y K C E V I E G L E 1 150
V V V A L D L Q G V 1 156 L Q G V V F P Y F P 1 187 V I A S F D Q L
Y D 1 198 W R G G L D W C N A 1 202 L D W C N A G W L S 1 204 W C N
A G W L S D G 1 205 C N A G W L S D G C 1 206 N A G W L S D G S V 1
211 S D G S V Q Y P I T 1 226 C G G Q N T V P G V 1 233 P G V R N Y
G F W D 1 235 V R N Y G F W D K D 1 260 R F Y Y L I H P T K 1 282 D
G A Q I A K V G Q 1 285 Q X A K V G Q I F A 1 293 F A A W K I L G Y
D 1 301 Y D R C D A G W L A 1 338 P D K K H K L Y G V 1 342 H K L Y
G V Y C F R 1 345 Y G V Y C F R A Y N 1 151P3D4 v.2: HLA Peptide
Scoring Results B*4402 10-mers SYFPEITHI 79 D E K Q R K D K V L 23
2 L E H T T K T F P L 22 185 E E K R K E K A E I 21 98 C E G I N I
S G S F 20 192 A E I H Y R K N K Q 18 278 A A S P A A W L P L 18 45
G I I T Q G A K D F 17 7 K T F P L R A L H I 16 209 A E K N M K K K
I D 16 211 K N M K K K I D K Y 16 233 G F I F K T I A P L 16 371 A
G S G Y C G A L W 16 5 T T K T F P L R A L 15 80 E K Q R K D K V L
L 15 106 S F C R N K L K Y L 15 193 E I H Y R K N K Q L 15 282 A A
W L P L R T P W 15 295 S S C P T S S S T Y 15 58 Q F V G S Y K L A
Y 14 68 S N D G E H W T V Y 14 105 G S F C R N K L K Y 14 157 A S E
A Y K K V C L 14 184 L E E K R K E K A E 14 221 T E S P G G G S P R
14 223 S P G G G S P R G L 14 230 R G L G F I F K T I 14 261 G S S
A H R P P A L 14 275 P V P A A S P A A W 14 320 R H S P S G G G G L
14 377 G A L W K A I E S L 14 381 K A I E S L E E G L 14 386 L E E
G L G G K Q K 14 387 E E G L G G K Q K D 14 29 M K Q D K K V D L L
13 50 G A K D F G H V Q F 13 103 I S G S F C R N K L 13 108 C R N K
L K Y L A F 13 122 M N T N P S R R P Y 13 131 Y H F Q V P S R I F
13 152 C P Q G H A S E A Y 13 158 S E A Y K K V C L S 13 171 H E V
G W K Y Q A V 13 226 G G S P R G L G F I 13 307 L S P Y G P R N P L
13 335 H C Q G Q K H N V L 13 355 S E N N S W Y V E N 13 362 V E N
G R P A D L A 13 374 G Y C G A L W K A I 13 383 I E S L E E G L G G
13 399 R K A E N G P H L L 13 28 K M K Q D K K V D L 12 37 L L V P
T K V T G I 12 109 R N K L K Y L A F L 12 124 T N P S R R P Y H F
12 132 H F Q V P S R I F W 12 168 G A P H E V G W K Y 12 175 W K Y
Q A V T A T L 12 187 K R K E K A E I H Y 12 196 Y R K N K Q L M R L
12 227 G S P R G L G F I F 12 301 S S T Y D S L S P Y 12 351 R K P
K S E N N S W 12 361 Y V E N G R P A D L 12 370 L A G S G Y C G A L
12 398 E R K A E N G P H L 12 18 V E S I R D H S G Q 11 38 L V P T
K V T G I I 11 54 F 6 H V Q F V G S Y 11 56 H V Q F V G S Y K L 11
166 L S G A P H E V G W 11 189 K E K A E I H Y R K 11 208 Q A E K N
M K K K I 11 225 G G G S P R G L G F 11 276 V P A A S P A A W L 11
298 P T S S S T Y D S L 11 352 K P K S E N N S W Y 11 366 R P A D L
A G S G Y 11 397 K E R K A E N G P H 11 12 R A L H I V V E S I 10
65 L A Y S N D G E H W 10 71 G E H W T V Y Q D E 10 143 Q E K A D G
G S C C 10 92 K A V V V S C E G I 9 94 V V V S C E G I N I 9 130 P
Y H F Q V P S R I 9 241 P L A A T R A T R I 9 264 A H R P P A L S A
R 9 274 A P V P A A S P A A 8 283 A W L P L R T P W T 8 19 E S I R
D H S G Q K 7 182 A T L E E K R K E K 7 272 A R A P V P A A S P 7
306 S L S P Y G P R N P 7 314 N P L P N P R H S P 7 393 K Q K D K E
R K A E 7 35 V D L L V P T K V T 6 66 A Y S N D G E H W T 6 85 D K
V L L G R K A V 6 99 E G I N I S G S F C 6 116 A F L H K R M N T N
6 127 S R R P Y H F Q V P 6 133 F Q V P S R I F W R 6 138 R I F W R
Q E K A D 6 215 K K I D K Y T E S P 6 232 L G F I F K T I A P 6 237
K T I A P L A A T R 6 239 I A P L A A T R A T 6 240 A P L A A T R A
T R 6 243 A A T R A T R I G H 6 244 A T R A T R I G H P 6 269 A L S
A R A P V P A 6 279 A S P A A W L P L R 6 345 A R G K P Q R K P K 6
363 E N G R P A D L A G 6 388 E G L G G K Q K D K 6 3 E H T T K T F
P L R 5 10 P L R A L H I V V E 5 23 D H S G Q K M K Q D 5 34 K V D
L L V P T K V S 40 P T K V T G I I T Q 5 41 T K V T G I I T Q G 5
51 A K D F G H V Q F V 5 52 K D F G H V Q F V G 5 57 V Q F V G S Y
K L A 5 87 V L L G R K A V V V 5 95 V V S C E G I N I S 5 97 S C E
G I N I S G S 5 104 S G S F C R N K L K 5 123 N T N P S R R P Y H 5
137 S R I F W R Q E K A 5 146 A D G G S C C P Q G 5 167 S G A P H E
V G W K 5 169 A P H E V G W K Y Q 5 200 K Q L M R L Q K Q A 5 229 P
R G L G F I F K T 5 235 I F K T I A P L A A 5 252 H P G G R T P R A
G 5 260 A G S S A H R P P A 5 266 R P P A L S A R A P 5 309 P Y G P
R N P L P N 5 322 S P S G G G G L K K 5 323 P S G G G G L K K P 5
333 A R H C Q G Q K H N 5 364 N 6 R P A D L A 6 S 5 8 T F P L R A L
H I V 4 9 F P L R A L H I V V 4 14 L H I V V E S I R D 4 15 H I V V
E S I R D H 4 27 Q K M K Q D K K V D 4 30 K Q D K K V D L L V 4 33
K K V D L L V P T K 4 44 T 6 I I T Q G A K D 4 77 Y Q D E K Q R K D
K 4 81 K Q R K D K V L L G 4 86 K V L L G R K A V V 4 88 L L G R K
A V V V S 4 101 I N I S G S F C R N 4 102 N I S G S F C R N K 4 110
N K L K Y L A F L H 4 112 L K Y L A F L H K R 4 113 K Y L A F L H K
R M 4 115 L A F L H K R M N T 4 120 K R M N T N P S R R 4 125 N P S
R R P Y H F Q 4 135 V P S R I F W R Q E 4 150 S C C P Q G H A S E 4
156 H A S E A Y K K V C 4 160 A Y K K V C L S G A 4 179 A V T A T L
E E K R 4 188 R K E K A E T H Y R 4 190 E K A E I H Y R K W 4 191 K
A E I H Y R K N K 4 198 K N K Q L M R L Q K 4 199 N K Q L M R L Q K
Q 4 201 Q L M R L Q K Q A E 4 207 K Q A E K N M K K K 4 222 E S P G
G G S P R G 4 228 S P R G L G F I F K 4 234 F I F K T I A P L A 4
238 T I A P L A A T R A 4 247 A T R I G H P G G R 4 248 T R I G H P
G G R T 4 250 I G H P G G R T P R 4 256 R T P R A G S S A H 4 263 S
A H R P P A L S A 4 265 H R P P A L S A R A 4 270 L S A R A P V P A
A 4 271 S A R A P V P A A C 4 284 W L P L R T P W T R 4 287 L R T P
W T R P S S 4 291 W T R P S S C P T C 4 300 S S S T Y D S L S P 4
313 R N P L P N P R H S 4 324 S 6 G G G L K K P A 4 325 L K K P A R
H C Q G 4 337 Q G Q K H N V L A R 4 346 R G K P Q R K P K S 4 347 G
K P Q R K P K S E 4 350 Q R K P K S E N N S 4 368 A D L A G S G Y C
G 4 378 A L W K A I E S L E 4 382 A I E S L E E G L G 4 384 E S L E
E G L G G K 4 11 L R A L H I V V E S 3 13 A L H I V V E S I R 3 20
S I R D H S G Q K M 3 21 I R D H S G Q K M K 3 26 G Q K M K Q D K K
V 3 31 Q D K K V D L L V P 3 36 D L L V P T K V T G 3 42 K V T G I
I T Q G A 3 62 S Y K L A Y S N D G 3 69 N D G E H W T V Y Q 3 72 E
H W T V Y Q D E K 3 74 W T V Y Q D E K Q R 3 76 V Y Q D E K Q R K D
3 82 Q R K D K V L L G R 3 84 K D K V L L G R K A 3 93 A V V V S C
E G I N 3 111 K L K Y L A F L H K 3
118 L H K R M N T N P S 3 144 E K A D G G S C C P 3 145 K A D G G S
C C P Q 3 149 G S C C P Q G H A C 3 155 G H A S E A Y K K V 3 159 E
A Y K K V C L S G 3 163 K V C L S G A P H E 3 164 V C L S G A P H E
V 3 165 C L S G A P H E V G 3 172 E V G W K Y Q A V T 3 173 V G W K
Y Q A V T A 3 174 G W K Y Q A V T A T 3 176 K Y Q A V T A T L E 3
180 V T A T L E E K R K 3 181 T A T L E E K R K E 3 186 E K R K E K
A E I H 3 203 M R L Q K Q A E K N 3 210 E K N M K K K I D K 3 212 N
M K K K I D K Y T 3 224 P G G G S P R G L G 3 236 F K T I A P L A A
T 3 242 L A A T R A T R I G 3 251 G H P G G R T P R A 3 255 G R T P
R A G S S A 3 258 P R A G S S A H R P 3 262 S S A H R P P A L C 3
268 P A L S A R A P V P 3 280 S P A A W L P L R T 3 281 P A A W L P
L R T P 3 286 P L R T P W T R P S 3 296 S C P T S S S T Y D 3 308 S
P Y G P R N P L P 3 310 Y 6 P R N P L P N P 3 311 G P R N P L P N P
R 3 312 P R N P L P N P R H 3 316 L P N P R H S P S G 3 317 P N P R
H S P S G G 3 325 G 6 G G L K K P A R 3 327 G G L K K P A R H C 3
331 K P A R H C Q G Q K 3 339 Q K H N V L A R G K 3 340 K H N V L A
R G K P 3 341 H N V L A R G K P Q 3 342 N V L A R G K P Q R 3 344 L
A R G K P Q R K P 3 354 K S E N N S W Y V E 3 356 E N N S W Y V E N
G 3 357 N N S W Y V E N G R 3 360 W Y V E N G R P A D 3 373 S G Y C
G A L W K A 3 376 C G A L W K A I E S 3 4 H T T K T F P L R A 2 6 T
K T F P L R A L H 2 25 S 6 Q K M K Q D K K 2 32 D K K V D L L V P T
2 43 V T G I I T Q G A K 2 49 Q 6 A K D F G H V Q 2 53 D F G H V Q
F V G c 2 60 V G S Y K L A Y S N 2 67 Y S N D G E H W T V 2 70 D G
E H W T V Y Q D 2 83 R K D K V L L G R K 2 89 L G R K A V V V S C 2
107 F C R N K L K Y L A 2 121 R M N T N P S R R P 2 126 P S R R P Y
H F Q V 2 128 R R P Y H F Q V P S 2 134 Q V P S R I F W R Q 2 151 C
C P Q G H A S E A 2 154 Q G H A S E A Y K K 2 161 Y K K V C L S G A
P 2 177 Y Q A V T A T L E E 2 178 Q A V T A T L E E K 2 194 I H Y R
K N K Q L M 2 197 R K N K Q L M R L Q 2 204 R L Q K Q A E K N M 2
216 K I D K Y T E S P G 2 218 D K Y T E S P G G G 2 245 T R A T R I
G H P G 2 249 R I G H P G G R T P 2 253 P G G R T P R A G S 2 254 G
G R T P R A G S S 2 267 P P A L S A R A P V 2 273 R A P V P A A S P
A 2 277 P A A S P A A W L P 2 285 L P L R T P W T R P 2 288 R T P W
T R P S S C 2 292 T R P S S C P T S S 2 293 R P S S C P T S S S 2
299 T S S S T Y D S L S 2 302 S T Y D S L S P Y G 2 303 T Y D S L S
P Y G P 2 304 Y D S L S P Y G P R 2 315 P L P N P R H S P S 2 321 H
S P S G G G G L K 2 326 G G G L K K P A R H 2 328 G L K K P A R H C
Q 2 330 K K P A R H C Q G Q 2 336 C Q G Q K H N V L A 2 343 V L A R
G K P Q R K 2 348 K P Q R K P K S E N 2 359 S W Y V E N G R P A 2
365 G R P A D L A G S G 2 367 P A D L A G S G Y C 2 372 G S G Y C G
A L W K 2 385 S L E E G L G G K Q 2 389 G L G G K Q K D K E 2 390 L
G G K Q K D K H R 2 392 G K Q K D K E R K A 2 395 K D K E R K A E N
G 2 396 D K E R K A E N G P 2 16 I V V E S I R D H S 1 17 V V E S I
R D H S G 1 22 R D H S G Q K M K Q 1 39 V P T K V T G I I T 1 47 I
T Q G A K D F G H 1 48 T Q G A K D F G H V 1 59 F V G S Y K L A Y S
1 63 Y K L A Y S N D G E 1 64 K L A Y S N D G E H 1 73 H W T V Y Q
D E K Q 1 78 Q D E K Q R K D K V 1 90 G R K A V V V S C E 1 96 V S
C E G I N I S G 1 114 Y L A F L H K R M N 1 129 R P Y H F Q V P S R
1 136 P S R I F W R Q E K 1 139 I F W R Q E K A D G 1 140 F W R Q E
K A D G G 1 147 D G G S C C P Q G H 1 148 G G S C C P Q G H A 1 162
K K V C L S G A P H 1 170 P H E V G W K Y Q A 1 183 T L E E K R K E
K A 1 195 H Y R K N K Q L M R 1 202 L M R L Q K Q A E K 1 205 L Q K
Q A E K N M K 1 206 Q K Q A E K N M K K 1 213 M K K K I D K Y T E 1
214 K K K I D K Y T E S 1 219 K Y T E S P G G G S 1 246 R A T R I G
H P G G 1 259 R A G S S A H R P P 1 289 T P W T R P S S C P 1 290 P
W T R P S S C P T 1 294 P S S C P T S S S T 1 297 C P T S S S T Y D
S 1 305 D S L S P Y G P R N 1 318 N P R H S P S G G G 1 332 P A R H
C Q G Q K H 1 334 R H C Q G Q K H N V 1 338 G Q K H N V L A R G 1
353 P K S E N N S W Y V 1 358 N S W Y V E N G R P 1 369 D L A G S G
Y C G A 1 379 L W K A I E S L E E 1 380 W K A I E S L E E G 1 394 Q
K D K E R K A E N 1
[0847]
54TABLE XLVII SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4:
HLA Peptide Scoring Results B*5101 10-mers SYFPEITHI NO DATA
[0848]
55TABLE XLVIII SEQ. ID Pos 1 2 3 4 5 6 1 8 9 0 1 2 3 4 5 score NO.
151P3D4 v.1: HLA Peptide Scoring Results DRB1*0101 15-mers
SYFPEITHI 78 R I K W T K L T S D Y L K E V 35 259 G R F Y Y L I H P
T K L T Y D 33 61 C K F Y R D P T A F G S G I H 30 214 S V Q Y P I
T K P R E P C G G 28 7 L V L I S I C W A D H L S D N 27 27 D R A I
H I Q A E N G P H L L 27 102 K K T Y G G Y Q G R V F L K G 27 148 D
T V V V A L D L Q G V V F P 27 161 P P Y F P R L G R Y N L N F H 27
169 R Y N L N F H E A Q Q A C L D 27 109 Q G R V F L K G G S D S D
A S 26 267 P T K L T Y D E A V Q A C L N 26 298 I L G Y D R C D A G
W L A D G 26 1 M K S L L L L V L I S I C W A 25 39 H L L V E A E Q
A K V F S H R 25 139 C E V I E G L E D D T V V V A 25 283 G A Q I A
K V G Q I F A A W K 25 4 L L L L V L I S I C W A D H L 24 21 N Y T
L D H D R A I H I Q A E 24 29 A I H I Q A E N G P H L L V E 24 36 N
G P H L L V E A E Q A K V F 24 46 Q A K V F S H R G G N V T L P 24
150 V V V A L D L Q G V V F P Y F 24 151 V V A L D L Q G V V F P Y
F P 24 199 R G G L D W C N A G W L S D G 24 229 Q N T V P G V R N Y
G F W D K 24 86 S D Y L K E V D V F V S M G Y 23 145 L E D D T V V
V A L D L Q G V 23 293 F A A W K I L G Y D R C D A G 23 3 S L L L L
V L I S I C W A D H 22 153 A L D L Q G V V F P Y F P R L 22 178 Q Q
A C L D Q D A V I A S F D 22 286 I A K V G Q I F A A W K I L G 22
19 S D N Y T L D H D R A I H I Q 21 134 Y G R Y K C E V I E G L E D
D 21 74 I H K I R I K W T K L T S D Y 20 85 T S D Y L K E V D V F V
S M G 20 154 L D L Q G V V F P Y F P R L G 20 235 V R N Y G F W D K
D K S R Y D 20 260 R F Y Y L I H P T K L T Y D E 20 287 A K V 6 Q I
F A A W K I L G Y 20 313 S V R Y P I S R P R R R C S P 20 38 P H L
L V E A E Q A K V F S H 19 47 A K V F S H R G G N V T L P C 19 92 V
D V F V S M G Y H K K T Y G 19 110 G R V F L K G G S D S D A S L 19
160 V F P Y F P R L G R Y N L N F 19 238 Y G F W D K D K S R Y D V
F C 19 250 V F C F T S N F N G R F Y Y L 19 254 T S N F N G R F Y Y
L I H P T 19 264 L I H P T K L T Y D E A V Q A 19 63 F Y R D P T A
F G S G I H K I 18 81 W T K L T S D Y L K E V D V F 18 108 Y Q G R
V F L K G G S D S D A 18 131 L E D Y G R Y K C E V I E G L 18 156 L
Q G V V F P Y F P R L G R Y 18 171 N L N F H E A Q Q A C L D Q D 18
188 I A S F D Q L Y D A W R G G L 18 191 F D Q L Y D A W R G G L D
W C 18 192 D Q L Y D A W R G G L D W C N 18 258 N G R F Y Y L I H P
T K L T Y 18 269 K L T Y D E A V Q A C L N D G 18 273 D E A V Q A C
L N D G A Q I A 18 299 L G Y D R C D A G W L A D G S 18 302 D R C D
A G W L A D G S V R Y 18 329 E A A V R F V G F P D K K H K 18 338 P
D K K H K L Y G V Y C F R A 18 56 N V T L P C K F Y R D P T A F 17
71 G S G I H K I R I K W T K L T 17 111 R V F L K G G S D S D A S L
V 17 118 S D S D A S L V I T D L T L E 17 123 S L V I T D L T L E D
Y G R Y 17 149 T V V V A L D L Q G V V F P Y 17 206 N A G W L S D G
S V Q Y P I T 17 275 A V Q A C L N D G A Q I A K V 17 276 V Q A C L
N D G A Q I A K V G 17 305 D A G W L A D G S V R Y P I S 17 306 A G
W L A D G S V R Y P I S R 17 311 D G S V R Y P I S R P R R R C 17
315 R Y P I S R P R R R C S P T E 17 319 S R P R R R C S P T E A A
V R 17 11 S I C W A D H L S D N Y T L D 16 18 L S D N Y T L D H D R
A I H I 16 52 H R G G N V T L P C K F Y R D 16 60 P C K F Y R D P T
A F G S G I 16 73 G I H K I R I K W T K L T S D 16 83 K L T S D Y L
K E V D V F V S 16 89 L K E V D V F V S M G Y H K K 16 91 E V D V F
V S M G Y H K K T Y 16 114 L K G G S D S D A S L V I T D 16 142 I E
G L E D D T V V V A L D L 16 166 R L G R Y N L N F H E A Q Q A 16
176 E A Q Q A C L D Q D A V I A S 16 179 Q A C L D Q D A V I A S F
D Q 16 196 D A W R G G L D W C N A G W L 16 200 G G L D W C N A G W
L S D G S 16 203 D W C N A G W L S D G S V Q Y 16 204 W C N A G W L
S D G S V Q Y P 16 207 A G W L S D G S V Q Y P I T K 16 246 S R Y D
V F C F T S N F N G R 16 282 D G A Q I A K V G Q I F A A W 16 292 I
F A A W K I L G Y D R C D A 16 295 A W K I L G Y D R C D A G W L 16
303 R C D A G W L A D G S V R Y P 16 320 R P R R R C S P T E A A V
R F 16 323 R R C S P T E A A V R F V G F 16 326 S P T E A A V R F V
G F P D K 16 2 K S L L L L V L I S I C W A D 15 30 I H I Q A E N G
P H L L V E A 15 59 L P C K F Y R D P T A F G S G 15 103 K T Y S G
Y Q G R V F L K G G 15 136 R Y K C E V I E G L E D D T V 15 157 Q G
V V F P Y F P R L G R Y N 15 212 D G S V Q Y P I T K P R E P C 15
226 C G G Q N T V P G V R N Y G F 15 279 C L N D G A Q I A K V G Q
I F 15 6 L L V L I S I C W A D H L S D 14 15 A D H L S D N Y T L D
H D R A 14 26 H D R A I H I Q A E N G P H L 14 40 L L V E A E Q A K
V F S H R G 14 43 E A E Q A K V F S H R G G N V 14 68 T A F G S G I
H K I R I K W T 14 97 S M G Y H K K T Y G G Y Q G R 14 112 V F L K
G G S D S D A S L V I 14 115 K G G S D S D A S L V I T D L 14 120 S
D A S L V I T D L T L E D Y 14 122 A S L V I T D L T L E D Y G R 14
141 V I E G L E D D T V V V A L D 14 172 L N F H E A Q Q A C L D Q
D A 14 181 C L D Q D A V I A S F D Q L Y 14 244 D K S R Y D V F C F
T S N F N 14 247 R Y D V F C F T S N F N G R F 14 270 L T Y D E A V
Q A C L N D G A 14 308 W L A D G S V R Y P I S R P R 14 119 D S D A
S L V I T D L T L E D 13 121 D A S L V I T D L T L E D Y G 13 331 A
V R F V G F P D K K H K L Y 13 336 G F P D K K H K L Y G V Y C F 13
107 G Y Q G R V F L K G G S D S D 12 158 G V V F P Y F P R L G R Y
N L 12 167 L G R Y N L N F H E A Q Q A C 12 182 L D Q D A V I A S F
D Q L Y D 12 183 D Q D A V X A S F D Q L Y D A 12 195 Y D A W R G G
L D W C N A G W 12 210 L S D G S V Q Y P I T K P R E 12 223 R E P C
G G Q N T V P G V R N 12 290 G Q I F A A W K I L G Y D R C 12 5 L L
L V L I S I C W A D H L S 11 49 V F S H R G G N V T L P C K F 11 67
P T A F G S G I H K I R I K W 11 93 D V F V S M G Y H K K T Y G G
11 98 M G Y H K K T Y G G Y Q G R V 11 105 Y G G Y Q G R V F L K G
G S D 11 125 V I T D L T L E D Y G R Y K C 11 201 G L D W C N A G W
L S D G S V 11 211 S D G S V Q Y P I T K P R E P 11 216 Q Y P I T K
P R E P C G G Q N 11 232 V P G V R N Y G F W D K D K S 11 245 K S R
Y D V F C F T S N F N G 11 248 Y D V F C F T S N F N G R F Y 11 256
N F N G R F Y Y L I H P T K L 11 281 N D G A Q I A K V G Q I F A A
11 334 F V G F P D K K H K L Y G V Y 11 339 D K K H K L Y G V Y C F
R A Y 11 53 R G G N V T L P C K F Y R D P 10 54 G G N V T L P C K F
Y R D P T 10 58 T L P C K F Y R D P T A F G S 10 66 D P T A F G S G
I H K I R I K 10 75 H K I R I K W T K L T S D Y L 10 76 K I R I K W
T K L T S D Y L K 10 84 L T S D Y L K E V D V F V S M 10 99 G Y H K
K T Y G G Y Q G R V F 10 126 I T D L T L E D Y G R Y K C E 10 128 D
L T L E D Y G R Y K C E V I 10 140 E V I E G L E D D T V V V A L 10
217 Y P I T K P R E P C G G Q N T 10 219 I T K P R E P C G G Q N T
V P 10 224 E P C G G Q N T V P G V R N Y 10 237 N Y G F W D K D K S
R Y D V F 10 240 F W D K D K S R Y D V F C F T 10 265 I H P T K L T
Y D E A V Q A C 10 288 K V G Q I F A A W K I L G Y D 10 316 y P I S
R P R R R C S P T E A 10 324 R C S P T E A A V R F V G F P 10 332 V
R F V G F P D K K H K L Y G 10 13 C W A D H L S D N Y T L D H D 9
35 E N G P H L L V E A E Q A K V 9 48 K V F S H R G G N V T L P C K
9 65 R D P T A F G S G I H K I R I 9 95 F V S M G Y H K K T Y G G Y
Q 9 106 G G Y Q G R V F L K G G S D S 9 127 T D L T L E D Y G R Y K
C E V 9 147 D D T V V V A L D L Q G V V F 9 177 A Q Q A C L D Q D A
V I A S F 9 186 A V I A S F D Q L Y D A W R G 9 189 A S F D Q L Y D
A W R G G L D 9 193 Q L Y D A W R G G L D W C N A 9 205 C N A G W L
S D G S V Q Y P I 9 220 T K P R E P C G G Q N T V P G 9 221 K P R E
P C G G Q N T V P G V 9 222 P R E P C G G Q N T V P G V R 9 231 T V
P G V R N Y G F W D K D K 9 239 G F W D K D K S R Y D V F C F 9 251
F C F T S N F N G R F Y Y L I 9 262 Y Y L I H P T K L T Y D E A V 9
277 Q A C L N D G A Q I A K V G Q 9 278 A C L N D G A Q I A K V G Q
I 9 284 A Q I A K V G Q I F A A W K I 9 304 C D A G W L A D G S V R
Y P I 9 310 A D G S V R Y P I S R P R R R 9 322 R R R C S P T E A A
V R F V G 9 328 T E A A V R F V G F P D K K H 9 333 R F V G F P D K
K H K L Y G V 9 8 V L I S I C W A D H L S D N Y 8 9 L I S I C W A D
H L S D N Y T 8 12 I C W A D H L S D N Y T L D H 8 23 T L D H D R A
I H I Q A E N G 8 24 L D H D R A I H I Q A E N G P 8 31 H I Q A E N
G P H L L V E A E 8 33 Q A E N G P H L L V E A E Q A 8 34 A E N G P
H L L V E A E Q A K 8 37 G P H L L V E A E Q A K V F S 8 64 Y R D P
T A F G S G I H K I R 8 87 D Y L K E V D V F V S M G Y H 8 90 K E V
D V F V S M G Y H K K T 8 96 V S M G Y H K K T Y G G Y Q G 8 101 H
K K T Y G G Y Q G R V F L K 8 113 F L K G G S D S D A S L V I T 8
130 T L E D Y G R Y K C E V I E G 8 138 K C E V I E G L E D D T V V
V 8 143 E G L E D D T V V V A L D L Q 8 163 Y F P R L G R Y N L N F
H E A 8 164 F P R L G R Y N L N F H E A Q 8 175 H E A Q Q A C L D Q
D A V I A 8 180 A C L D Q D A V I A S F D Q L 8 184 Q D A V I A S F
D Q L Y D A W 8 185 D A V I A S F D Q L Y D A W R 8 208 G W L S D G
S V Q Y P I T K P 8 242 D K D K S R Y D V F C F T S N 8 253 F T S N
F N G R F Y Y L I H P 8 261 F Y Y L I H P T K L T Y D E A 8 274 E A
V Q A C L N D G A Q I A K 8 280 L N D G A Q I A K V G Q I F A 8 289
V G Q I F A A W K I L G Y D R 8 296 W K I L G Y D R C D A G W L A 8
307 G W L A D G S V R Y P I S R P 8 318 I S R P R R R C S P T E A A
V 8 321 P R R R C S P T E A A V R F V 8 327 P T E A A V R F V G F P
D K K 8 88 Y L K E V D V F V S M G Y H K 7 146 E D D T V V V A L D
L Q G V V 7 285 Q I A K V G Q I F A A W K I L 7 330 A A V R F V G F
P D K K H K L 7 50 F S H R G G N V T L P C K F Y 6 51 S H R G G N V
T L P C K F Y R 6 77 I R I K W T K L T S D Y L K E 6 135 G R Y K C
E V I E G L E D D T 6 144 G L E D D T V V V A L D L Q G 6 173 N F H
E A Q Q A C L D Q D A V 6 187 V I A S F D Q L Y D A W R G G 6 209 W
L S D G S V Q Y P I T K P R 6 213 G S V Q Y P I T K P R E P C G 6
225 P C G G Q N T V P G V R N Y G 6 263 Y L I H P T K L T Y D E A V
Q 6 271 T Y D E A V Q A C L N D G A Q 6 309 L A D G S V R Y P I S R
P R R 6 312 G S V R Y P I S R P R R R C S 6 137 Y K C E V I E G L E
D D T V V 5 44 A E Q A K V F S H R G G N V T 4 45 E Q A K V F S H R
G G N V T L 4 69 A F G S G I H K I R I K W T K 4 72 S G I H K I R I
K W T K L T S 4 100 Y H K K T Y G G Y Q G R V F L 4 25 D H D R A I
H I Q A E N G P H 3 133 D Y G R Y K C E V I E G L E D 3 162 P Y F P
R L G R Y N L N F H E 3 190 S F D Q L Y D A W R G G L D W 3 227 G G
Q N T V P G V R N Y G F W 3 252 C F T S N F N G R F Y Y L I H 3 57
V T L P C K F Y R D P T A F G 2 79 I K W T K L T S D Y L K E V D 2
132 E D Y G R Y K C E V I E G L E 2 165 P R L G R Y N L N F H E A Q
Q 2 198 W R G G L D W C N A G W L S D 2 218 P I T K P R E P C G G Q
N T V 2 233 P G V R N Y G F W D K D K S R 2 243 K D K S R Y D V F C
F T S N F 2 249 D V F C F T S N F N G R F Y Y 2 294 A A W K I L G Y
D R C D A G W 2 297 K I L G Y D R C D A G W L A D 2 335 V G F P D K
K H K L Y G V Y C 2 14 W A D H L S D N Y T L D H D R 1 17 H L S D N
Y T L D H D R A I H 1 28 R A I H I Q A E N G P H L L V 1 32 I Q A E
N G P H L L V E A E Q 1 70 F G S G I H K I R I K W T K L 1 80 K W T
K L T S D Y L K E V D V 1 94 V F V S M G Y H K K T Y G G Y 1 124 L
V I T D L T L E D Y G R Y K 1 129 L T L E D Y G R Y K C E V I E 1
155 D L Q G V V F P Y F P R L G R 1 159 V V F P Y F P R L G R Y N L
N 1 194 L Y D A W R G G L D W C N A G 1 197 A W R G G L D W C N A G
W L S 1 202 L D W C N A G W L S D G S V Q 1 228 G Q N T V P G V R N
Y G F W D 1 234 G V R N Y G F W D K D K S R Y 1 236 R N Y G F W D K
D K S R Y D V 1 241 W D K D K S R Y D V F C F T S 1 272 Y D E A V Q
A C L N D G A Q I 1 300 G Y D R C D A G W L A D G S V 1 314 V R Y P
I S R P R R R C S P T 1 337 P P D K K H K L Y G V Y C F R 1 TABLE
XLVIII 151P3D4 v.2: HLA Peptide Scoring Results DRB1*0101 15-mers
SYFPEITHI 301 S S T Y D S L S P Y G P R N P 34 32 D K K V D L L V P
T K V T G I 33 236 F K T I A P L A A T R A T R I 33 43 V T G I I T
Q G A K D F G H V 32 40 P T K V T G I I T Q G A K D F 31 54 F G H V
Q F V G S Y K L A Y S 31 128 R R P Y H F Q V P S R I F W R 31 233 G
F I F K T I A P L A A T R A 31 158 S E A Y K K V C L S G A P H E 29
217 I D K Y T E S P G G G S P R G 29 18 V E S I R D H S G Q K M K Q
D 27 82 Q R K D K V L L G R K A V V V 27 357 N N S W Y V E N G R P
A D L A 27 51 A K D F G H V Q F V G S Y K L 26 92 K A V V V S C E G
I N I S G S 26 232 L G F I F K T I A P L A A T R 26 247 A T R I G H
P G G R T P R A G 26 174 G W K Y Q A V T A T L E E K R 25 202 L M R
L Q K Q A E K N M K K K 25 239 I A P L A A T R A T R I G H P 25 264
A H R P P A L S A R A P V P A 25 284 W L P L R T P W T R P S S C P
25 5 T T K T F P L R A L H I V V E 24 85 D K V L L G R K A V V V S
C E 24 119 H K R M N T N P S R R P Y H F 24 229 P R G L G F I F K T
I A P L A 24 281 P A A W L P L R T P W T R P S 24 304 Y D S L S P Y
G P R N P L P N 24 377 G A L W K A I E S L E E G L G 24 36 D L L V
P T K V T G I I T Q G 22 138 R I F W R Q E K A D G G S C C 22 267 P
P A L S A R A P V P A A S P 22 270 L S A R A P V P A A S P A A W 22
359 S W Y V E N G R P A D L A G S 22 116 A F L H K R M N T N P S R
R P 21 129 R P Y H F Q V P S R I F W R Q 21 35 V D L L V P T K V T
G I I T Q 20 83 R K D K V L L G R K A V V V S 20 6 T K T F P L R A
L H I V V E S 19 98 C E G I N X S G S F C R N K L 19 104 S G S F C
R N K L K Y L A F L 19 106 S F C R N K L K Y L A F L H K 19 111 K L
K Y L A F L H K R M N T N 19 115 L A F L H K R M N T N P S R R 19
231 G L G F I F K T I A P L A A T 19 318 N P R H S P S G G G G L K
K P 19 367 P A D L A G S G Y C G A L W K 19 372 G S G Y C G A L W K
A I E S L 19 8 T F P L R A L H I V V E S I R 18 60 V G S Y K L A Y
S N D G E H W 18 112 L K Y L A F L H K R M N T N P 18 161 y K K V C
L S G A P H E V G W 18 171 H E V G W K Y Q A V T A T L E 18 172 E V
G W K Y Q A V T A T L E E 18 223 S P G G G S P R G L G F I F K 18
252 H P G G R T P R A G S S A H R 18 338 G Q K H N V L A R G K P Q
R K 18 364 N G R P A D L A G S G Y C G A 18 384 E S L E E G L G G K
Q K D K E 18 2 L E H T T K T F P L R A L H I 17 11 L R A L H I V V
E S I R D H S 17 14 L H I V V E S I R D H S G Q K 17 26 G Q K M K Q
D K K V D L L V P 17 29 M K Q D K K V D L L V P T K V 17 37 L L V P
T K V T G I I T Q G A 17 76 V Y Q D E K Q R K D K V L L G 17 84 K D
K V L L G R K A V V V S C 17 90 G R K A V V V S C E G I N I S 17 93
A V V V S C E G I N I S G S F 17 96 V S C E G I N I S G S F C R N
17 109 R N K L K Y L A P L H K R M N 17 137 S R I F W R Q E K A D G
G S C 17 160 A Y K K V C L S G A P H E V G 17 181 T A T L E E K R K
E K A E I H 17 191 K A E I H Y R K N K Q L M R L 17 200 K Q L M R L
Q K Q A E K N M K 17 218 D K Y T E S P G G G S P R G L 17 221 T E S
P G G G S P R G L G F I 17 230 R G L G F I F K T I A P L A A 17 253
P G G R T P R A G S S A H R P 17 279 A S P A A W L P L R T P W T R
17 288 R T P W T R P S S C P T S S S 17 337 Q G Q K H N V L A R G K
P Q R 17 360 W Y V K N G R P A D L A G S G 17 374 G Y C G A L W K A
I E S L E E 17 380 W K A I E S L E E G L G G K Q 17 383 I E S L E H
G L G G K Q K D K 17 396 D K E R K A E N G P H L L V E 17 57 V Q F
V G S Y K L A Y S N D G 16 86 K V L L G R K A V V V S C E G 16 95 V
V S C E G I N I S G S F C R 16 147 D G G S C C P Q G H A S E A Y 16
149 G S C C P Q G H A S E A Y K K 16 199 N K Q L M R L Q K Q A E K
N M 16 225 G G G S P R G L G F I F K T I 16 256 R T P R A G S S A H
R P P A L 16 261 G S S A H R P P A L S A R A P 16 266 R P P A L S A
R A P V P A A S 16 269 A L S A R A P V P A A S P A A 16 271 S A R A
P V P A A S P A A W L 16 274 A P V P A A S P A A W L P L R 16 275 P
V P A A S P A A W L P L R T 16 307 L S P Y G P R N P L P N P R H 16
311 G P R N P L P N P R H S P S G 16 313 R N P L P N P R H S P S G
G G 16 344 L A
R G K P Q R K P K S E N N 16 142 R Q E K A D G G S C C P Q G H 15
159 E A Y K K V C L S G A P H E V 15 272 A R A P V P A A S P A A W
L P 15 282 A A W L P L R T P W T R P S S 15 290 P W T R P S S C P T
S S S T Y 15 295 S S C P T S S S T Y D S L S P 15 356 E N N S W Y V
E N G R P A D L 15 397 K E R K A E N G P H L L V E A 15 10 P L R A
L H I V V E S I R D H 14 15 H I V V E S I R D H S G Q K M 14 33 K K
V D L L V P T K V T G I I 14 97 S C E G I N I S G S F C R N K 14
122 M N T N P S R R P Y H F Q V P 14 162 K K V C L S G A P H E V G
W K 14 173 V G W K Y Q A V T A T L E E K 14 193 E I H Y R K N K Q L
M R L Q K 14 213 M K K K I D K Y T E S P G G G 14 249 R I G H P G G
R T P R A G S S 14 259 R A G S S A H R P P A L S A R 14 260 A G S S
A H R P P A L S A R A 14 263 S A H R P P A L S A R A P V P 14 273 R
A P V P A A S P A A W L P L 14 287 L R T P W T R P S S C P T S S 14
291 W T R P S S C P T S S S T Y D 14 298 P T S S S T Y D S L S P Y
G P 14 333 A R H C Q G Q K H N V L A R G 14 341 H N V L A R G K P Q
R K P K S 14 351 R K P K S E N N S W Y V E N G 14 12 R A L H I V V
E S I R D H S G 13 212 N M K K K I D K Y T E S P G G 13 245 T R A T
R I G H P G G R T P R 13 24 H S G Q K M K Q D K K V D L L 12 42 K V
T G I I T Q G A K D F G H 12 71 G E H W T V Y Q D E K Q R K D 12 74
W T V Y Q D E K Q R K D K V L 12 89 L G R K A V V V S C E G I N I
12 184 L E E K R K E K A E I H Y R K 12 206 Q K Q A E K N M K K K I
D K Y 12 210 E K N M K K K I D K Y T E S P 12 342 N V L A R G K P Q
R K P K S E 12 358 N S W Y V E N G R P A D L A G 12 362 V E N G R P
A D L A G S G Y C 12 381 K A I E S L E E G L G G K Q K 12 390 L G G
K Q K D K E R K A E N G 12 56 H V Q F V G S Y K L A Y S N D 11 64 K
L A Y S N D G E H W T V Y Q 11 226 G G S P R G L G F I F K T I A 11
321 H S P S G G G G L K K P A R H 11 325 G G G G L K K P A R H C Q
G Q 11 326 G G G L K K P A R H C Q G Q K 11 330 K K P A R H C Q G Q
K H N V L 11 339 Q K H N V L A R G K P Q R K P 11 3 E H T T K T F P
L R A L H I V 10 13 A L H I V V E S I R D H S G Q 10 28 K M K Q D K
K V D L L V P T K 10 47 I T Q G A K D F G H V Q F V G 10 48 T Q G A
K D F G H V Q F V G S 10 59 F V G S Y K L A Y S N D G E H 10 65 L A
Y S N D G E H W T V Y Q D 10 77 Y Q D E K Q R K D K V L L G R 10
105 G S F C R N K L K Y L A F L H 10 107 F C R N K L K Y L A F L H
K R 10 108 C R N K L K Y L A F L H K R M 10 114 Y L A F L H K R M N
T N P S R 10 124 T N P S R R P Y H F Q V P S R 10 125 N P S R R P Y
H F Q V P S R I 10 130 P Y H F Q V P S R I F W R Q E 10 135 V P S R
I F W R Q E K A D G G 10 139 I F W R Q E K A D G G S C C P 10 140 F
W R Q E K A D G G S C C P Q 10 141 W R Q K K A D G G S C C P Q G 10
152 C P Q G H A S E A Y K K V C L 10 153 P Q G H A S E A Y K K V C
L S 10 177 Y Q A V T A T L E E K R K E K 10 178 Q A V T A T L E E K
R K E K A 10 183 T L E E K R K E K A E I H Y R 10 195 H Y R K N K Q
L M R L Q K Q A 10 198 K N K Q L M R L Q K Q A E K N 10 214 K K K I
D K Y T E S P G G G S 10 215 K K I D K Y T E S P G G G S P 10 242 L
A A T R A T R I G H P G G R 10 244 A T R A T R I G H P G G R T P 10
251 G H P G G R T P R A G S S A H 10 289 T P W T R P S S C P T S S
S T 10 316 L P N P R H S P S G G G G L K 10 317 P N P R H S P S G G
G G L K K 10 320 R H S P S G G G G L K K P A R 10 347 6 K P Q R K P
K S E N N S W Y 10 376 C G A L W K A I E S L E E G L 10 379 L W K A
I E S L E E G L G G K 10 394 Q K D K E R K A E N G P H L L 10 9 F P
L R A L H I V V E S I R D 9 23 D H S G Q K M K Q D K K V D L 9 25 S
G Q K M K Q D K K V D L L V 9 31 Q D K K V D L L V P T K V T G 9 41
T K V T G I I T Q G A K D F G 9 44 T G I I T Q G A K D F G H V Q 9
49 Q G A K D F G H V Q F V G S Y 9 53 D F G H V Q F V G S Y K L A Y
9 55 G H V Q F V G S Y K L A Y S N 9 73 H W T V Y Q D E K Q R K D K
V 9 91 R K A V V V S C E G I N I S G 9 100 G I N I S G S F C R N K
L K Y 9 101 I N I S G S F C R N K L K Y L 9 136 P S R I F W R Q E K
A D G G S 9 166 L S G A P H E V G W K Y Q A V 9 169 A P H E V G W K
Y Q A V T A T 9 194 I H Y R K N K Q L M R L Q K Q 9 196 Y R K N K Q
L M R L Q K Q A E 9 201 Q L M R L Q K Q A E K N M K K 9 211 K N M K
K K I D K Y T E S P G 9 219 K Y T E S P G G G S P R G L G 9 224 P G
G G S P R G L G F I F K T 9 228 S P R G L G F I F K T I A P L 9 257
T P R A G S S A H R P P A L S 9 265 H R P P A L S A R A P V P A A 9
283 A W L P L R T P W T R P S S C 9 285 L P L R T P W T R P S S C P
T 9 310 Y G P R N P L P N P R H S P S 9 319 P R H S P S G G G G L K
K P A 9 322 S P S G G G G L K K P A R H C 9 340 K H N V L A R G K P
Q R K P K 9 348 K P Q R K P K S E N N S W Y V 9 370 L A G S G Y C G
A L W K A I E 9 371 A G S G Y C G A L W K A I E S 9 387 E E G L G G
K Q K D K E R K A 9 388 E G L G G K Q K D K E R K A E 9 393 K Q K D
K E R K A E N G P H L 9 7 K T F P L R A L H I V V E S I 8 27 Q K M
K Q D K K V D L L V P T 8 34 K V D L L V P T K V T G I I T 8 46 I I
T Q G A K D F G H V Q F V 8 58 Q F V G S Y K L A Y S N D G E 8 62 S
Y K L A Y S N D G E H W T V 8 63 y K L A Y S N D G E H W T V Y 8 72
E H W T V Y Q D E K Q R K D K 8 78 Q D E K Q R K D K V L L G R K 8
81 K Q R K D K V L L G R K A V V 8 126 P S R R P Y H F Q V P S R I
F 8 132 H F Q V P S R I F W R Q E K A 8 145 K A D G G S C C P Q G H
A S E 8 146 A D G G S C C P Q G H A S E A 8 155 G H A S E A Y K K V
C L S G A 8 156 K A S E A Y K K V C L S G A P 8 163 K V C L S G A P
H E V G W K Y 8 167 S G A P H E V G W K Y Q A V T 8 168 G A P H E V
G W K Y Q A V T A 8 170 P H E V G W K Y Q A V T A T L 8 188 R K E K
A E I H Y R K N K Q L 8 192 A E I H Y R K N K Q L M R L Q 8 197 R K
N K Q L M R L Q K Q A E K 8 207 K Q A E K N M K K K I D K Y T 8 216
K I D K Y T E S P G G G S P R 8 235 I F K T I A P L A A T R A T R 8
237 K T I A P L A A T R A T R I G 8 243 A A T R A T R I G H P G G R
T 8 246 R A T R I G H P G G R T P R A 8 255 G R T P R A G S S A H R
P P A 8 258 P R A G S S A H R P P A L S A 8 268 P A L S A R A P V P
A A S P A 8 276 V P A A S P A A W L P L R T P 8 296 S C P T S S S T
Y D S L S P Y 8 297 C P T S S S T Y D S L S P Y G 8 303 T Y D S L S
P Y G P R N P L P 8 305 D S L S P Y G P R N P L P N P 8 306 S L S P
Y G P R N P L P N P R 8 308 S P Y G P R N P L P N P R H S 8 309 P Y
G P R N P L P N P R H S P 8 312 P R N P L P N P R H S P S G G 8 315
P L P N P R H S P S G G G G L 8 323 P S G G G G L K K P A R H C Q 8
331 K P A R H C Q G Q K H N V L A 8 332 P A R H C Q G Q K H N V L A
R 8 334 R H C Q G Q K H N V L A R G K 8 363 E N G R P A D L A G S G
Y C G 8 365 G R P A D L A G S G Y C G A L 8 366 R P A D L A G S G Y
C G A L W 8 368 A D L A G S G Y C G A L W K A 8 369 D L A G S G Y C
G A L W K A I 8 373 S G Y C G A L W K A I E S L E 8 375 Y C G A L W
K A I E S L E E G 8 398 E R K A E N G P H L L V E A E 8 400 K A E N
G P H L L V E A E Q A 8 21 I R D H S G Q K M K Q D K K V 7 88 L L G
R K A V V V S C E G I N 7 133 F Q V P S R I F W R Q E K A D 7 148 G
G S C C P Q G H A S E A Y K 7 220 Y T E S P G G G S P R G L G F 7
240 A P L A A T R A T R I G H P G 7 250 I G H P G G R T P R A G S S
A 7 254 G G R T P R A G S S A H R P P 7 294 P S S C P T S S S T Y D
S L S 7 314 N P L P N P R H S P S G G G G 7 324 S G G G G L K K P A
R H C Q G 7 345 A R G K P Q R K P K S E N N S 7 17 V V E S I R D H
S G Q K M K Q 6 52 K D F G H V Q F V G S Y K L A 6 67 Y S N D G E H
W T V Y Q D E K 6 70 D G E H W T V Y Q D E K Q R K 6 118 L H K R M
N T N P S R R P Y H 6 150 S C C P Q G H A S E A Y K K V 6 175 W K Y
Q A V T A T L E E K R K 6 278 A A S P A A W L P L R T P W T 6 286 P
L R T P W T R P S S C P T S 6 292 T R P S S C P T S S S T Y D S 6
293 R P S S C P T S S S T Y D S L 6 300 S S S T Y D S L S P Y G P R
N 6 16 I V V E S I R D H S G Q K M K 5 134 Q V P S R I F W R Q E K
A D G 5 179 A V T A T L E E K R K E K A E 5 395 K D K E R K A E N G
P H L L V 5 79 D E K Q R K D K V L L G R K A 4 87 V L L G R K A V V
V S C E G I 4 189 K E K A E I H Y R K N K Q L M 4 234 F I F K T I A
P L A A T R A T 4 80 E K Q R K D K V L L G R K A V 3 117 F L H K R
M N T N P S R R P Y 3 182 A T L E E K R K E K A E I H Y 3 186 E K R
K E K A E I H Y R K N K 3 209 A E K N M K K K I D K Y T E S 3 241 P
L A A T R A T R I G H P G G 3 343 V L A R G K P Q R K P K S E N 3
349 P Q R K P K S E N N S W Y V E 3 378 A L W K A I E S L E E G L G
G 3 382 A I E S L E E G L G G K Q K D 3 385 S L E E G L G G K Q K D
K E R 3 391 G G K Q K D K E R K A E N G P 3 4 H T T K T F P L R A L
H I V V 2 19 E S I R D H S G Q K M K Q D K 2 38 L V P T K V T G I I
T Q G A K 2 39 V P T K V T G I I T Q G A K D 2 45 G I I T Q G A K D
F G H V Q F 2 61 G S Y K L A Y S N D G E H W T 2 102 N I S G S F C
R N K L K Y L A 2 110 N K L K Y L A F L H K R M N T 2 120 K R M N T
N P S R R P Y H F Q 2 157 A S E A Y K K V C L S G A P H 2 164 V C L
S G A P H E V G W K Y Q 2 203 M R L Q K Q A E K N M K K K I 2 205 L
Q K Q A E K N M K K K I D K 2 208 Q A E K N M K K K I D K Y T E 2
227 G S P R G L G F I F K T I A P 2 248 T R I G H P G G R T P R A G
S 2 262 S S A H R P P A L S A R A P V 2 280 S P A A W L P L R T P W
T R P 2 328 G L K K P A R H C Q G Q K H N 2 335 H C Q G Q K H N V L
A R G K P 2 355 S E N N S W Y V E N G R P A D 2 392 G K Q K D K E R
K A E N G P H 2 1 M L E H T T K T F P L R A L H 1 20 S I R D H S G
Q K M K Q D K K 1 30 K Q D K K V D L L V P T K V T 1 66 A Y S N D G
E H W T V Y Q D E 1 75 T V Y Q D E K Q R K D K V L L 1 103 I S G S
F C R N K L K Y L A F 1 113 K Y L A F L H K R M N T N P S 1 121 R M
N T N P S R R P Y H F Q V 1 131 Y H F Q V P S R I F W R Q E K 1 154
Q G H A S E A Y K K V C L S G 1 165 C L S G A P H E V G W K Y Q A 1
176 K Y Q A V T A T L E E K R K E 1 180 V T A T L E E K R K E K A E
I 1 185 E E K R K E K A E I H Y R K N 1 187 K R K E K A E I H Y R K
N K Q 1 190 E K A E I H Y R K N K Q L M R 1 204 R L Q K Q A E K N M
K K K I D 1 299 T S S S T Y D S L S P Y G P R 1 302 S T Y D S L S P
Y G P R N P L 1 327 G G L K K P A R H C Q G Q K H 1 336 C Q G Q K H
N V L A R G K P Q 1 350 Q R K P K S E N N S W Y V E N 1 353 P K S E
N N S W Y V E N G R P 1 354 K S E N N S W Y V E N G R P A 1 386 L E
E G L G G K Q K D K E R K 1 389 G L G G K Q K D K E R K A E N 1 399
R K A E N G P H L L V E A E Q 1
[0849]
56TABLE XLIX SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 score NO.
151P3D4 v.1: HLA Peptide Scoring Results DRB1*0301 15 - mers
SYFPEITHI 149 T V V V A L D L Q G V V F P Y 28 333 R F V G F P D K
K H K L Y G V 27 261 F Y Y L I H P T K L T Y D E A 26 161 F P Y F P
R L G R Y N L N F H 24 171 N L N F H E A Q Q A C L D Q D 24 191 F D
Q L Y D A W R G G L D W C 24 229 Q N T V P G V R N Y G F W D K 24
250 V F C F T S N F N G R F Y Y L 24 122 A S L V I T D L T L E D Y
G R 23 206 N A G W L S D G S V Q Y P I T 23 267 P T K L T Y D E A V
Q A C L N 23 81 W T K L T S D Y L K E V D V F 22 237 N Y G F W D K
D K S R Y D V F 22 305 D A G W L A D G S V R Y P I S 22 38 P H L L
V E A E Q A K V F S H 21 113 F L K G G S D S D A S L V I T 21 142 I
E G L E D D T V V V A L D L 21 179 Q A C L D Q D A V I A S F D Q 21
184 Q D A V I A S F D Q L Y D A W 21 296 W K I L G Y D R C D A G W
L A 21 21 N Y T L D H D R A I H I Q A E 20 37 G P H L L V E A E Q A
K V F S 20 60 P C K F Y R D P T A F G S G I 20 126 I T D L T L E D
Y G R Y K C E 20 123 S L V I T D L T L E D Y G R Y 19 138 K C E V I
E G L E D D T V V V 19 156 L Q G V V F P Y F P R L G R Y 19 7 L V L
I S I C W A D H L S D N 18 29 A I H I Q A E N G P H L L V E 18 39 H
L L V E A E Q A K V F S H R 18 54 G G N V T L P C K F Y R D P T 18
89 L K E V D V F V S M G Y H K K 18 128 D L T L E D Y G R Y K C E V
I 18 153 A L D L Q G V V F P Y F P R L 18 163 Y F P R L G R Y N L N
F H E A 18 185 D A V I A S F D Q L Y D A W R 18 199 R G G L D W C N
A G W L S D G 18 290 G Q I F A A W K I L G Y D R C 18 295 A W K I L
G Y D R C D A G W L 18 334 F V G F P D K K H K L Y G V Y 18 27 D R
A I H I Q A E N G P H L L 17 95 F V S M G Y H K K T Y G G Y Q 17
216 Q Y P I T K P R E P C G G Q N 17 273 D E A V Q A C L N D G A Q
I A 17 277 Q A C L N D G A Q I A K V G Q 17 283 G A Q I A K V G Q I
F A A W K 17 289 V G Q I F A A W K I L G Y D R 17 48 K V F S H R G
G N V T L P C K 16 103 K T Y G G Y Q G R V F L K G G 16 158 G V V F
P Y F P R L G R Y N L 16 248 Y D V F C F T S N F N G R F Y 16 269 K
L T Y D E A V Q A C L N D G 16 315 R Y P I S R P R R R C S P T E 16
332 V R F V G F P D K K H K L Y G 16 13 C W A D H L S D N Y T L D H
D 15 252 C F T S N F N G R F Y Y L I H 15 2 K S L L L L V L I S I C
W A D 14 14 W A D H L S D N Y T L D H D R 14 94 V F V S M G Y H K K
T Y G G Y 14 141 V I E G L E D D T V V V A L D 14 276 V Q A C L N D
G A Q I A K V G 14 1 M K S L L L L V L I S I C W A 13 4 L L L L V L
I S I C W A D H L 13 5 L L L V L I S I C W A D H L S 13 6 L L V L I
S I C W A D H L S D 13 19 S D N Y T L D H D R A I H I Q 13 127 T D
L T L E D Y G R Y K C E V 13 147 D D T V V V A L D L Q G V V F 13
151 V V A L D L Q G V V F P Y F P 13 197 A W R G G L D W C N A G W
L S 13 3 S L L L L V L I S I C W A D H 12 46 Q A K V F S H R G G N
V T L P 12 74 I H K I R I K W T K L T S D Y 12 76 K I R I K W T K L
T S D Y L K 12 86 S D Y L K E V D V F V S M G Y 12 92 V D V F V S M
G Y H K K T Y G 12 93 D V F V S M G Y H K K T Y G G 12 109 Q G R V
F L K G G S D S D A S 12 111 R V F L K G G S D S D A S L V 12 115 K
G G S D S D A S L V I T D L 12 121 D A S L V I T D L T L E D Y G 12
148 D T V V V A L D L Q G V V F P 12 157 Q G V V F P Y F P R L G R
Y N 12 169 R Y N L N F H E A Q Q A C L D 12 177 A Q Q A C L D Q D A
V I A S F 12 190 S F D Q L Y D A W R G G L D W 12 207 A G W L S D G
S V Q Y P I T K 12 232 V P G V R N Y G F W D K D K S 12 262 Y Y L I
H P T K L T Y D E A V 12 299 L G Y D R C D A G W L A D G S 12 329 E
A A V R F V G F P D K K H K 12 9 L I S I C W A D H L S D N Y T 11
15 A D H L S D N Y T L D H D R A 11 30 I H I Q A E N G P H L L V E
A 11 73 G I H K I R I K W T K L T S D 11 87 D Y L K E V D V F V S M
G Y H 11 110 G R V F L K G G S D S D A S L 11 120 S D A S L V I T D
L T L E D Y 11 139 C E V I E G L E D D T V V V A 11 150 V V V A L D
L Q G V V F P Y F 11 164 F P R L G R Y N L N F H E A Q 11 227 G G Q
N T V P G V R N Y G F W 11 236 R N Y G F W D K D K S R Y D V 11 238
Y G F W D K D K S R Y D V F C 11 243 K D K S R Y D V F C F T S N F
11 247 R Y D V F C F T S N F N G R F 11 286 I A K V G Q I F A A W K
I L G 11 306 A G W L A D G S V R Y P I S R 11 311 D G S V R Y P I S
R P R R R C 11 331 A V R F V G F P D K K H K L Y 11 339 D K K H K L
Y G V Y C F R A Y 11 10 I S I C W A D H L S D N Y T L 10 11 S I C W
A D H L S D N Y T L D 10 47 A K V F S H R G G N V T L P C 10 52 H R
G G N V T L P C K F Y R D 10 53 R G G N V T L P C K F Y R D P 10 56
N V T L P C K F Y R D P T A F 10 71 G S G I H K I R I K W T K L T
10 84 L T S D Y L K E V D V F V S M 10 91 E V D V F V S M G Y H K K
T Y 10 143 E G L E D D T V V V A L D L Q 10 145 L E D D T V V V A L
D L Q G V 10 152 V A L D L Q G V V F P Y F P R 10 183 D Q D A V I A
S F D Q L Y D A 10 186 A V I A S F D Q L Y D A W R G 10 212 D G S V
Q Y P I T K P R E P C 10 246 S R Y D V F C F T S N F N G R 10 259 G
R F Y Y L I H P T K L T Y D 10 282 D G A Q I A K V G Q I F A A W 10
337 F P D K K H K L Y G V Y C F R 10 20 D N Y T L D H D R A I H I Q
A 9 59 L P C K F Y R D P T A F G S G 9 67 P T A F G S G I H K I R I
K W 9 77 I R I K W T K L T S D Y L K E 9 78 R I K W T K L T S D Y L
K E V 9 118 S D S D A S L V I T D L T L E 9 134 Y G R Y K C E V I E
G L E D D 9 168 G R Y N L N F H E A Q Q A C L 9 180 A C L D Q D A V
I A S F D Q L 9 188 I A S F D Q L Y D A W R G G L 9 198 W R G G L D
W C N A G W L S D 9 228 G Q N T V P G V R N Y G F W D 9 254 T S N F
N G R F Y Y L I H P T 9 266 H P T K L T Y D E A V Q A C L 9 288 K V
G Q I F A A W K I L G Y D 9 314 V R Y P I S R P R R R C S P T 9 321
P R R R C S P T E A A V R F V 9 323 R R C S P T E A A V R F V G F 9
326 S P T E A A V R F V G F P D K 9 28 R A I H I Q A E N G P H L L
V 8 35 E N G P H L L V E A E Q A K V 8 40 L L V E A E Q A K V F S H
R G 8 70 F G S G I H K I R I K W T K L 8 75 H K I R I K W T K L T S
D Y L 8 83 K L T S D Y L K E V D V F V S 8 97 S M G Y H K K T Y G G
Y Q G R 8 102 K K T Y G G Y Q G R V F L K G 8 107 G Y Q G R V F L K
G G S D S D 8 124 L V I T D L T L E D Y G R Y K 8 132 E D Y G R Y K
C E V I E G L E 8 135 G R Y K C E V I E G L E D D T 8 159 V V F P Y
F P R L G R Y N L N 8 165 P R L G R Y N L N F H E A Q Q 8 170 Y N L
N F H E A Q Q A C L D Q 8 215 V Q Y P I T K P R E P C G G Q 8 221 K
P R E P C G G Q N T V P G V 8 239 G F W D K D K S R Y D V F C F 8
240 F W D K D K S R Y D V F C F T 8 242 D K D K S R Y D V F C F T S
N 8 251 F C F T S N F N G R F Y Y L I 8 253 F T S N F N G R F Y Y L
I H P 8 258 N G R F Y Y L I H P T K L T Y 8 298 I L G Y D R C D A G
W L A D G 8 312 G S V R Y P I S R P R R R C S 8 316 Y P I S R P R R
R C S P T E A 8 25 D H D R A I H I Q A E N G P H 7 45 E Q A K V F S
H R G G N V T L 7 72 S G I H K I R I K W T K L T S 7 82 T K L T S D
Y L K E V D V F V 7 176 E A Q Q A C L D Q D A V I A S 7 213 G S V Q
Y P I T K P R E P C G 7 235 V R N Y G F W D K D K S R Y D 7 280 L N
D G A Q I A K V G Q I F A 7 335 V G F P D K K H K L Y G V Y C 7 57
V T L P C K F Y R D P T A F G 6 68 T A F G S G I H K I R I K W T 6
101 H K K T Y G G Y Q G R V F L K 6 130 T L E D Y G R Y K C E V I E
G 6 208 G W L S D G S V Q Y P I T K P 6 222 P R E P C G G Q N T V P
G V R 6 307 G W L A D G S V R Y P I S R P 6 325 C S P T E A A V R F
V G F P D 6 36 N G P H L L V E A E Q A K V F 4 55 G N V T L P C K F
Y R D P T A 4 79 I K W T K L T S D Y L K E V D 4 80 K W T K L T S D
Y L K E V D V 4 162 P Y F P R L G R Y N L N F H E 4 220 T K P R E P
C G G Q N T V P G 4 260 R F Y Y L I H P T K L T Y D E 4 24 L D H D
R A I H I Q A E N G P 3 31 H I Q A E N G P H L L V E A E 3 33 Q A E
N G P H L L V E A E Q A 3 85 T S D Y L K E V D V F V S M G 3 100 Y
H K K T Y G G Y Q G R V F L 3 125 V I T D L T L E D Y G R Y K C 3
178 Q Q A C L D Q D A V I A S F D 3 211 S D G S V Q Y P I T K P R E
P 3 217 Y P I T K P R E P C G G Q N T 3 241 W D K D K S R Y D V F C
F T S 3 265 I H P T K L T Y D E A V Q A C 3 285 Q I A K V G Q I F A
A W K I L 3 300 G Y D R C D A G W L A D G S V 3 320 R P R R R C S P
T E A A V R F 3 322 R R R C S P T E A A V R F V G 3 8 V L I S I C W
A D H L S D N Y 2 12 I C W A D H L S D N Y T L D H 2 26 H D R A I H
I Q A E N G P H L 2 34 A E N G P H L L V E A E Q A K 2 44 A E Q A K
V F S H R G G N V T 2 49 V F S H R G G N V T L P C K F 2 64 Y R D P
T A F G S G I H K I R 2 66 D P T A F G S G I H K I R I K 2 90 K E V
D V F V S M G Y H K K T 2 99 G Y H K K T Y G G Y Q G R V F 2 105 Y
G G Y Q G R V F L K G G S D 2 108 Y Q G R V F L K G G S D S D A 2
116 G G S D S D A S L V I T D L T 2 119 D S D A S L V I T D L T L E
D 2 136 R Y K C E V I E G L E D D T V 2 137 Y K C E V I E G L E D D
T V V 2 144 G L E D D T V V V A L D L Q G 2 146 E D D T V V V A L D
L Q G V V 2 155 D L Q G V V F P Y F P R L G R 2 160 V F P Y F P R L
G R Y N L N F 2 167 L G R Y N L N F H E A Q Q A C 2 175 H E A Q Q A
C L D Q D A V I A 2 187 V I A S F D Q L Y D A W R G G 2 193 Q L Y D
A W R G G L D W C N A 2 195 Y D A W R G G L D W C N A G W 2 201 G L
D W C N A G W L S D G S V 2 219 I T K P R E P C G G Q N T V P 2 226
C G G Q N T V P G V R N Y G F 2 268 T K L T Y D E A V Q A C L N D 2
271 T Y D E A V Q A C L N D G A Q 2 272 Y D E A V Q A C L N D G A Q
I 2 275 A V Q A C L N D G A Q I A K V 2 278 A C L N D G A Q I A K V
G Q I 2 284 A Q I A K V G Q I F A A W K I 2 293 F A A W K I L G Y D
R C D A G 2 294 A A W K I L G Y D R C D A G W 2 310 A D G S V R Y P
I S R P R R R 2 319 S R P R R R C S P T E A A V R 2 324 R C S P T E
A A V R F V G F P 2 336 G F P D K K H K L Y G V Y C F 2 340 K K H K
L Y G V Y C F R A Y N 2 17 H L S D N Y T L D H D R A I H 1 32 I Q A
E N G P H L L V E A E Q 1 41 L V E A E Q A K V F S H R G G 1 50 F S
H R G G N V T L P C K F Y 1 58 T L P C K F Y R D P T A F G S 1 61 C
K F Y R D P T A F G S G I H 1 62 K F Y R D P T A F G S G I H K 1 65
R D P T A F G S G I H K I R I 1 69 A F G S G I H K I R I K W T K 1
88 Y L K E V D V F V S M G Y H K 1 96 V S M G Y H K K T Y G G Y Q G
1 98 M G Y H K K T Y G G Y Q G R V 1 104 T Y G G Y Q G R V F L K G
G S 1 112 V F L K G G S D S D A S L V I 1 114 L K G G S D S D A S L
V I T D 1 117 G S D S D A S L V I T D L T L 1 131 L E D Y G R Y K C
E V I E G L 1 133 D Y G R Y K C E V I E G L E D 1 140 E V I E G L E
D D T V V V A L 1 172 L N F H E A Q Q A C L D Q D A 1 173 N F H E A
Q Q A C L D Q D A V 1 189 A S F D Q L Y D A W R G G L D 1 192 D Q L
Y D A W R G G L D W C N 1 194 L Y D A W R G G L D W C N A G 1 196 D
A W R G G L D W C N A G W L 1 200 G G L D W C N A G W L S D G S 1
203 D W C N A G W L S D G S V Q Y 1 204 W C N A G W L S D G S V Q Y
P 1 205 C N A G W L S D G S V Q Y P I 1 209 W L S D G S V Q Y P I T
K P R 1 214 S V Q Y P I T K P R E P C G G 1 218 P I T K P R E P C G
G Q N T V 1 223 R E P C G G Q N T V P G V R N 1 231 T V P G V R N Y
G F W D K D K 1 233 P G V R N Y G F W D K D K S R 1 249 D V F C F T
S N F N G R F Y Y 1 255 S N F N G R F Y Y L I H P T K 1 256 N F N G
R F Y Y L I H P T K L 1 257 F N G R F Y Y L I H P T K L T 1 263 Y L
I H P T K L T Y D E A V Q 1 264 L I H P T K L T Y D E A V Q A 1 270
L T Y D E A V Q A C L N D G A 1 274 E A V Q A C L N D G A Q I A K 1
281 N D G A Q I A K V G Q I F A A 1 287 A K V G Q I F A A W K I L G
Y 1 292 I F A A W K I L G Y D R C D A 1 297 K I L G Y D R C D A G W
L A D 1 301 Y D R C D A G W L A D G S V R 1 302 D R C D A G W L A D
G S V R Y 1 304 C D A G W L A D G S V R Y P I 1 308 W L A D G S V R
Y P I S R P R 1 318 I S R P R R R C S P T E A A V 1 328 T E A A V R
F V G F P D K K H 1 330 A A V R F V G F P D K K H K L 1 338 P D K K
H K L Y G V Y C F R A 1 151P3D4 v.2: HLA Peptide Scoring Results
DRB1*0301 15 - mers SYFPEITHI 26 G Q K M K Q D K K V D L L V P 37
73 H W T V Y Q D E K Q R K D K V 28 56 H V Q F V G S Y K L A Y S N
D 25 191 K A E I H Y R K N K Q L M R L 25 43 V T G I I T Q G A K D
F G H V 20 54 F G H V Q F V G S Y K L A Y S 20 84 K D K V L L G R K
A V V V S C 20 200 K Q L M R L Q K Q A E K N M K 20 299 T S S S T Y
D S L S P Y G P R 20 34 K V D L L V P T K V T G I I T 19 177 Y Q A
V T A T L E E K R K E K 19 340 K H N V L A R G K P Q R K P K 19 359
S W Y V E N G R P A D L A G S 19 380 W K A I E S L E E G L G G K Q
19 14 L H I V V E S I R D H S G Q K 18 181 T A T L E E K R K E K A
E I H 18 199 N K Q L M R L Q K Q A E K N M 18 231 G L G F I F K T I
A P L A A T 18 390 L G G K Q K D K E R K A E N G 18 44 T G I I T Q
G A K D F G H V Q 17 64 K L A Y S N D G E H W T V Y Q 17 91 R K A V
V V S C E G I N I S G 17 101 I N I S G S F C R N K L K Y L 17 104 S
G S F C R N K L K Y L A F L 17 115 L A F L H K R M N T N P S R R 17
136 P S R I F W R Q E K A D G G S 17 170 P H E V G W K Y Q A V T A
T L 17 202 L M R L Q K Q A E K N M K K K 17 326 G G G L K K P A R H
C Q G Q K 17 376 C G A L W K A I E S L E E G L 17 379 L W K A I E S
L E E G L G G K 17 387 E E G L G G K Q K D K E R K A 17 11 L R A L
H I V V E S I R D H S 16 78 Q D E K Q R K D K V L L G R K 16 103 I
S G S F C R N K L K Y L A F 16 112 L K Y L A F L H K R M N T N P 16
120 K R M N T N P S R R P Y H F Q 16 137 S R I F W R Q E K A D G G
S C 16 155 G H A S E A Y K K V C L S G A 16 185 E E K R K E K A E I
H Y R K N 16 214 K K K I D K Y T E S P G G G S 16 229 P R G L G F I
F K T I A P L A 16 305 D S L S P Y G P R N P L P N P 16 350 Q R K P
K S E N N S W Y V E N 16 130 P Y H F Q V P S R I F W R Q E 15 18 V
E S I R D H S G Q K M K Q D 14 79 D E K Q R K D K V L L G R K A 14
85 D K V L L G R K A V V V S C E 14 92 K A V V V S C E G I N I S G
S 14 30 K Q D K K V D L L V P T K V T 13 35 V D L L V P T K V T G I
I T Q 13 57 V Q F V G S Y K L A Y S N D G 13 273 R A P V P A A S P
A A W L P L 13 304 Y D S L S P Y G P R N P L P N 13 383 I E S L E E
G L G G K Q K D K 13 8 T F P L R A L H I V V E S I R 12 13 A L H I
V V E S I R D H S G Q 12 32 D K K V D L L V P T K V T G I 12 40 P T
K V T G I I T Q G A K D F 12 93 A V V V S C E G I N I S G S F 12
109 R N K L K Y L A F L H K R M N 12 141 W R Q E K A D G G S C C P
Q G 12 161 Y K K V C L S G A P H E V G W 12 212 N M K K K I D K Y T
E S P G G 12 341 H N V L A R G K P Q R K P K S 12 3 E H T T K T F P
L R A L H I V 11 15 H I V V E S I R D H S G Q K M 11 17 V V E S I R
D H S G Q K M K Q 11 48 T Q G A K D F G H V Q F V G S 11 86 K V L L
G R K A V V V S C E G 11 98 C E G I N I S G S F C R N K L 11 100 G
I N I S G S F C R N K L K Y 11 106 S F C R N K L K Y L A F L H K 11
107 F C R N K L K Y L A F L H K R 11 114 Y L A F L H K R M N T N P
S R 11 119 H K R M N T N P S R R P Y H F 11 132 H F Q V P S R I F W
R Q E K A 11 163 K V C L S G A P H E V G W K Y 11 210 E K N M K K K
I D K Y T E S P 11 232 L G F I F K T I A P L A A T R 11 233 G F I F
K T I A P L A A T R A 11 236 F K T I A P L A A T R A T R I 11 247 A
T R I G H P G G R T P R A G 11 267 P P A L S A R A P V P A A S P 11
282 A A W L P L R T P W T R P S S 11 284 W L P L R T P W T R P S S
C P 11 348 K P Q R K P K S E N N S W Y V 11 363 E N G R P A D L A G
S G Y C G 11 367 P A D L A G S G Y C G A L W K 11 397 K E R K A E N
G P H L L V E A 11 4 H T T K T F P L R A L H I V V 10 27 Q K M K Q
D K K V D L L V P T 10 36 D L L V P T K V T G I I T Q G 10 47 I T Q
G A K D F G H V Q F V G 10 62 S Y K L A Y S N D G E H W T V 10 77 Y
Q D E K Q R K D K V L L G R 10 83 R K D K V L L G R K A V V V S 10
179 A V T A T L E E K R K E K A E 10 180 V T A T L E E K R K E K A
E I 10 198 K N K Q L M R L Q K Q A E K N 10 209 A E K N M K K K I D
K Y T E S 10 223 S P G G G S P R G L G F I F K 10 239 I A P L A A T
R A T R I G H P 10 274 A P V P A A S P A A W L P L R 10 276 V P A A
S P A A W L P L R T P 10 293 R P S S C P T S S S T Y D S L 10 312 P
R N P L P N P R H S P S G G 10 313 R N P L P N P R H S P S G G G 10
318 N P R H S P S G G G G L K K P 10 333 A R H C Q G Q K H N V L
A
R G 10 358 N S W Y V E N G R P A D L A G 10 368 A D L A G S G Y C G
A L W K A 10 375 Y C G A L W K A I E S L E E G 10 385 S L E E G L G
G K Q K D K E R 10 6 T K T F P L R A L H I V V E S 9 51 A K D F G H
V Q F V G S Y K L 9 61 G S Y K L A Y S N D G E H W T 9 105 G S F C
R N K L K Y L A F L H 9 113 K Y L A F L H K R M N T N P S 9 122 M N
T N P S R R P Y H F Q V P 9 129 R P Y H F Q V P S R I F W R Q 9 150
S C C P Q G H A S E A Y K K V 9 166 L S G A P H E V G W K Y Q A V 9
173 V G W K Y Q A V T A T L E E K 9 183 T L E E K R K E K A E I H Y
R 9 190 E K A E I H Y R K N K Q L M R 9 193 E I H Y R K N K Q L M R
L Q K 9 194 I H Y R K N K Q L M R L Q K Q 9 203 M R L Q K Q A E K N
M K K K I 9 221 T E S P G G G S P R G L G F I 9 225 G G G S P R G L
G F I F K T I 9 238 T I A P L A A T R A T R I G H 9 259 R A G S S A
H R P P A L S A R 9 296 S C P T S S S T Y D S L S P Y 9 342 N V L A
R G K P Q R K P K S E 9 344 L A R G K P Q R K P K S E N N 9 386 L E
E G L G G K Q K D K E R K 9 391 G G K Q K D K E R K A E N G P 9 396
D K E R K A E N G P H L L V E 9 20 S I R D H S G Q K M K Q D K K 8
23 D H S G Q K M K Q D K K V D L 8 52 K D F G H V Q F V G S Y K L A
8 66 A Y S N D G E H W T V Y Q D E 8 74 W T V Y Q D E K Q R K D K V
L 8 96 V S C E G I N I S G S F C R N 8 117 F L H K R M N T N P S R
R P Y 8 134 Q V P S R I F W R Q E K A D G 8 135 V P S R I F W R Q E
K A D G G 8 151 C C P Q G H A S E A Y K K V C 8 182 A T L E E K R K
E K A E I H Y 8 192 A E I H Y R K N K Q L M R L Q 8 196 Y R K N K Q
L M R L Q K Q A E 8 204 R L Q K Q A E K N M K K K I D 8 207 K Q A E
K N M K K K I D K Y T 8 208 Q A E K N M K K K I D K Y T E 8 222 E S
P G G G S P R G L G F I F 8 248 T R I G H P G G R T P R A G S 8 251
G H P G G R T P R A G S S A H 8 265 H R P P A L S A R A P V P A A 8
280 S P A A W L P L R T P W T R P 8 285 L P L R T P W T R P S S C P
T 8 310 Y G P R N P L P N P R H S P S 8 323 P S G G G G L K K P A R
H C Q 8 334 R H C Q G Q K H N V L A R G K 8 349 P Q R K P K S E N N
S W Y V E 8 364 N G R P A D L A G S G Y C G A 8 395 K D K E R K A E
N G P H L L V 8 19 E S I R D H S G Q K M K Q D K 7 22 R D H S G Q K
M K Q D K K V D 7 41 T K V T G I I T Q G A K D F G 7 72 E H W T V Y
Q D E K Q R K D K 7 75 T V Y Q D E K Q R K D K V L L 7 76 V Y Q D E
K Q R K D K V L L G 7 94 V V V S C E G I N I S G S F C 7 102 N I S
G S F C R N K L K Y L A 7 121 R M N T N P S R R P Y H F Q V 7 126 P
S R R P Y H F Q V P S R I F 7 146 A D G G S C C P Q G H A S E A 7
154 Q G H A S E A Y K K V C L S G 7 164 V C L S G A P H E V G W K Y
Q 7 178 Q A V T A T L E E K R K E K A 7 189 K E K A E I H Y R K N K
Q L M 7 206 Q K Q A E K N M K K K I D K Y 7 211 K N M K K K I D K Y
T E S P G 7 241 P L A A T R A T R I G H P G G 7 258 P R A G S S A H
R P P A L S A 7 306 S L S P Y G P R N P L P N P R 7 322 S P S G G G
G L K K P A R H C 7 331 K P A R H C Q G Q K H N V L A 7 332 P A R H
C Q G Q K H N V L A R 7 338 G Q K H N V L A R G K P Q R K 7 346 R G
K P Q R K P K S E N N S W 7 355 S E N N S W Y V E N G R P A D 7 356
E N N S W Y V E N G R P A D L 7 373 S G Y C G A L W K A I E S L E 7
389 G L G G K Q K D K E R K A E N 7 392 G K Q K D K E R K A E N G P
H 7 394 Q K D K E R K A E N G P H L L 7 25 S G Q K M K Q D K K V D
L L V 6 50 G A K D F G H V Q F V G S Y K 6 70 D G E H W T V Y Q D E
K Q R K 6 168 G A P H E V G W K Y Q A V T A 6 329 L K K P A R H C Q
G Q K H N V 6 343 V L A R G K P Q R K P K S E N 6 33 K K V D L L V
P T K V T G I I 4 108 C R N K L K Y L A F L H K R M 4 169 A P H E V
G W K Y Q A V T A T 4 234 F I F K T I A P L A A T R A T 4 382 A I E
S L E E G L G G K Q K D 4 393 K Q K D K E R K A E N G P H L 4 7 K T
F P L R A L H I V V E S I 3 24 H S G Q K M K Q D K K V D L L 3 42 K
V T G I I T Q G A K D F G H 3 60 V G S Y K L A Y S N D G E H W 3 82
Q R K D K V L L G R K A V V V 3 99 E G I N I S G S F C R N K L K 3
111 K L K Y L A F L H K R M N T N 3 125 N P S R R P Y H F Q V P S R
I 3 148 G G S C C P Q G H A S E A Y K 3 159 E A Y K K V C L S G A P
H E V 3 160 A Y K K V C L S G A P H E V G 3 162 K K V C L S G A P H
E V G W K 3 197 R K N K Q L M R L Q K Q A E K 3 201 Q L M R L Q K Q
A E K N M K K 3 217 I D K Y T E S P G G G S P R G 3 235 I F K T I A
P L A A T R A T R 3 255 G R T P R A G S S A H R P P A 3 260 A G S S
A H R P P A L S A R A 3 262 S S A H R P P A L S A R A P V 3 263 S A
H R P P A L S A R A P V P 3 266 R P P A L S A R A P V P A A S 3 269
A L S A R A P V P A A S P A A 3 270 L S A R A P V P A A S P A A W 3
272 A R A P V P A A S P A A W L P 3 281 P A A W L P L R T P W T R P
S 3 283 A W L P L R T P W T R P S S C 3 289 T P W T R P S S C P T S
S S T 3 295 S S C P T S S S T Y D S L S P 3 303 T Y D S L S P Y G P
R N P L P 3 309 P Y G P R N P L P N P R H S P 3 319 P R H S P S G G
G G L K K P A 3 320 R H S P S G G G G L K K P A R 3 324 S G G G G L
K K P A R H C Q G 3 325 G G G G L K K P A R H C Q G Q 3 330 K K P A
R H C Q G Q K H N V L 3 347 G K P Q R K P K S E N N S W Y 3 362 V E
N G R P A D L A G S G Y C 3 366 R P A D L A G S G Y C G A L W 3 377
G A L W K A I E S L E E G L G 3 381 K A I E S L E E G L G G K Q K 3
398 E R K A E N G P H L L V E A E 3 400 K A E N G P H L L V E A E Q
A 3 1 M L E H T T K T F P L R A L H 2 2 L E H T T K T F P L R A L H
I 2 5 T T K T F P L R A L H I V V E 2 9 F P L R A L H I V V E S I R
D 2 10 P L R A L H I V V E S I R D H 2 12 R A L H I V V E S I R D H
S G 2 28 K M K Q D K K V D L L V P T K 2 29 M K Q D K K V D L L V P
T K V 2 31 Q D K K V D L L V P T K V T G 2 38 L V P T K V T G I I T
Q G A K 2 55 G H V Q F V G S Y K L A Y S N 2 67 Y S N D G E H W T V
Y Q D E K 2 71 G E H W T V Y Q D E K Q R K D 2 80 E K Q R K D K V L
L G R K A V 2 87 V L L G R K A V V V S C E G I 2 90 G R K A V V V S
C E G I N I S 2 97 S C E G I N I S G S F C R N K 2 110 N K L K Y L
A F L H K R M N T 2 116 A F L H K R M N T N P S R R P 2 131 Y H F Q
V P S R I F W R Q E K 2 138 R I F W R Q E K A D G G S C C 2 145 K A
D G G S C C P Q G H A S E 2 152 C P Q G H A S E A Y K K V C L 2 153
P Q G H A S E A Y K K V C L S 2 156 H A S E A Y K K V C L S G A P 2
165 C L S G A P H E V G W K Y Q A 2 167 S G A P H E V G W K Y Q A V
T 2 172 E V G W K Y Q A V T A T L E E 2 184 L E E K R K E K A E I H
Y R K 2 188 R K E K A E I H Y R K N K Q L 2 195 H Y R K N K Q L M R
L Q K Q A 2 205 L Q K Q A E K N M K K K I D K 2 215 K K I D K Y T E
S P G G G S P 2 218 D K Y T E S P G G G S P R G L 2 219 K Y T E S P
G G G S P R G L G 2 224 P G G G S P R G L G F I F K T 2 226 G G S P
R G L G F I F K T I A 2 227 G S P R G L G F I F K T I A P 2 228 S P
R G L G F I F K T I A P L 2 230 R G L G F I F K T I A P L A A 2 237
K T I A P L A A T R A T R I G 2 244 A T R A T R I G H P G G R T P 2
246 R A T R I G H P G G R T P R A 2 253 P G G R T P R A G S S A H R
P 2 254 G G R T P R A G S S A H R P P 2 261 G S S A H R P P A L S A
R A P 2 264 A H R P P A L S A R A P V P A 2 268 P A L S A R A P V P
A A S P A 2 275 P V P A A S P A A W L P L R T 2 278 A A S P A A W L
P L R T P W T 2 288 R T P W T R P S S C P T S S S 2 291 W T R P S S
C P T S S S T Y D 2 297 C P T S S S T Y D S L S P Y G 2 301 S S T Y
D S L S P Y G P R N P 2 302 S T Y D S L S P Y G P R N P L 2 307 L S
P Y G P R N P L P N P R H 2 308 S P Y G P R N P L P N P R H S 2 316
L P N P R H S P S G G G G L K 2 317 P N P R H S P S G G G G L K K 2
321 H S P S G G G G L K K P A R H 2 327 G G L K K P A R H C Q G Q K
H 2 335 H C Q G Q K H N V L A R G K P 2 336 C Q G Q K H N V L A R G
K P Q 2 339 Q K H N V L A R G K P Q R K P 2 354 K S E N N S W Y V E
N G R P A 2 360 W Y V E N G R P A D L A G S G 2 361 Y V E N G R P A
D L A G S G Y 2 365 G R P A D L A G S G Y C G A L 2 369 D L A G S G
Y C G A L W K A I 2 370 L A G S G Y C G A L W K A I E 2 372 G S G Y
C G A L W K A I E S L 2 374 G Y C G A L W K A I E S L E E 2 21 I R
D H S G Q K M K Q D K K V 1 37 L L V P T K V T G I I T Q G A 1 39 V
P T K V T G I I T Q G A K D 1 45 G I I T Q G A K D F G H V Q F 1 49
Q G A K D F G H V Q F V G S Y 1 53 D F G H V Q F V G S Y K L A Y 1
58 Q F V G S Y K L A Y S N D G E 1 59 F V G S Y K L A Y S N D G E H
1 63 Y K L A Y S N D G E H W T V Y 1 65 L A Y S N D G E H W T V Y Q
D 1 69 N D G E H W T V Y Q D E K Q R 1 81 K Q R K D K V L L G R K A
V V 1 88 L L G R K A V V V S C E G I N 1 123 N T N P S R R P Y H F
Q V P S 1 124 T N P S R R P Y H F Q V P S R 1 139 I F W R Q E K A D
G G S C C P 1 142 R Q E K A D G G S C C P Q G H 1 143 Q E K A D G G
S C C P Q G H A 1 147 D G G S C C P Q G H A S E A Y 1 157 A S E A Y
K K V C L S G A P H 1 158 S E A Y K K V C L S G A P H E 1 171 H E V
G W K Y Q A V T A T L E 1 174 G W K Y Q A V T A T L E E K R 1 175 W
K Y Q A V T A T L E E K R K 1 176 K Y Q A V T A T L E E K R K E 1
186 E K R K E K A E I H Y R K N K 1 187 K R K E K A E I H Y R K N K
Q 1 213 M K K K I D K Y T E S P G G G 1 216 K I D K Y T E S P G G G
S P R 1 220 Y T E S P G G G S P R G L G F 1 242 L A A T R A T R I G
H P G G R 1 245 T R A T R I G H P G G R T P R 1 250 I G H P G G R T
P R A G S S A 1 252 H P G G R T P R A G S S A H R 1 256 R T P R A G
S S A H R P P A L 1 257 T P R A G S S A H R P P A L S 1 277 P A A S
P A A W L P L R T P W 1 279 A S P A A W L P L R T P W T R 1 287 L R
T P W T R P S S C P T S S 1 290 P W T R P S S C P T S S S T Y 1 294
P S S C P T S S S T Y D S L S 1 298 P T S S S T Y D S L S P Y G P 1
300 S S S T Y D S L S P Y G P R N 1 311 G P R N P L P N P R H S P S
G 1 314 N P L P N P R H S P S G G G G 1 315 P L P N P R H S P S G G
G G L 1 328 G L K K P A R H C Q G Q K H N 1 337 Q G Q K H N V L A R
G K P Q R 1 345 A R G K P Q R K P K S E N N S 1 351 R K P K S E N N
S W Y V E N G 1 352 K P K S E N N S W Y V E N G R 1 353 P K S E N N
S W Y V E N G R P 1 371 A G S G Y C G A L W K A I E S 1 378 A L W K
A I E S L E E G L G G 1 384 E S L E E G L G G K Q K D K E 1 388 E G
L G G K Q K D K E R K A E 1 399 R K A E N G P H L L V E A E Q 1
[0850]
57TABLE L SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 score NO.
151P3D4 v.1: HLA Peptide Scoring Results DRB1*0401 15-mers
SYFPEITHI 78 R I K W T K L T S D Y L K E V 28 161 F P Y F P R L G R
Y N L N F H 28 171 N L N F H E A Q Q A C L D Q D 28 258 N G R F Y Y
L I H P T K L T Y 28 269 K L T Y D E A V Q A C L N D G 28 38 P H L
L V E A E Q A K V F S H 26 149 T V V V A L D L Q G V V F P Y 26 191
F D Q L Y D A W R G G L D W C 26 247 R Y D V F C F T S N F N G R F
26 283 G A Q I A K V G Q I F A A W K 26 19 S D N Y T L D H D R A I
H I Q 22 60 P C K F Y R D P T A F G S G I 22 85 T S D Y L K E V D V
F V S M G 22 134 Y G R Y K C E V I E G L E D D 22 158 G V V F P Y F
P R L G R Y N L 22 167 L G R Y N L N F H E A Q Q A C 22 206 N A G W
L S D G S V Q Y P I T 22 238 Y G F W D K D K S R Y D V F C 22 245 K
S R Y D V F C F T S N F N G 22 259 G R F Y Y L I H P T K L T Y D 22
260 R F Y Y L I H P T K L T Y D E 22 305 D A G W L A D G S V R Y P
I S 22 1 M K S L L L L V L I S I C W A 20 3 S L L L L V L I S I C W
A D H 20 4 L L L L V L I S I C W A D H L 20 9 L I S I C W A D H L S
D N Y T 20 21 N Y T L D H D R A I H I Q A E 20 29 A I H I Q A E N G
P H L L V E 20 37 G P H L L V E A E Q A K V F S 20 71 G S G I H K I
R I K W T K L T 20 81 W T K L T S D Y L K E V D V F 20 86 S D Y L K
E V D V F V S M G Y 20 89 L K E V D V F V S M G Y H K K 20 93 D V F
V S M G Y H K K T Y G G 20 122 A S L V I T D L T L E D Y G R 20 139
C E V I E G L E D D T V V V A 20 142 I E G L E D D T V V V A L D L
20 148 D T V V V A L D L Q G V V F P 20 179 Q A C L D Q D A V I A S
F D Q 20 185 D A V I A S F D Q L Y D A W R 20 229 Q N T V P G V R N
Y G F W D K 20 267 P T K L T Y D E A V Q A C L N 20 273 D E A V Q A
C L N D G A Q I A 20 111 Q A C L N D G A Q I A K V G Q 20 286 I A K
V G Q I F A A W K I L G 20 295 A W K I L G Y D R C D A G W L 20 315
R Y P I S R P R R R C S P T E 20 329 E A A V R F V G F P D K K H K
20 18 L S D N Y T L D H D R A I H I 18 23 T L D H D R A I H I Q A E
N G 18 57 V T L P C K F Y R D P T A F G 18 115 K G G S D S D A S L
V I T D L 18 119 D S D A S L V I T D L T L E D 18 141 V I E G L E D
D T V V V A L D 18 176 E A Q Q A C L D Q D A V I A S 18 182 L D Q D
A V I A S F D Q L Y D 18 11 S I C W A D H L S D N Y T L D 16 61 C K
F Y R D P T A F G S G I H 16 67 P T A F G S G I H K I R I K W 16 92
V D V F V S M G Y H K K T Y G 16 110 G R V F L K G G S D S D A S L
16 131 L E D Y G R Y K C E V I E G L 16 188 I A S F D Q L Y D A W R
G G L 16 195 Y D A W R G G L D W C N A G W 16 201 G L D W C N A G W
L S D G S V 16 235 V R N Y G F W D K D K S R Y D 16 248 Y D V F C F
T S N F N G R F Y 16 250 V F C F T S N F N G R F Y Y L 16 293 F A A
W K I L G Y D R C D A G 16 298 I L G Y D R C D A G W L A D G 16 331
A V R F V G F P D K K H K L Y 16 74 I H K I R I K W T K L T S D Y
15 2 K S L L L L V L I S I C W A D 14 6 L L V L I S I C W A D H L S
D 14 7 L V L I S I C W A D H L S D N 14 15 A D H L S D N Y T L D H
D R A 14 39 H L L V E A E Q A K V F S H R 14 46 Q A K V F S H R G G
N V T L P 14 91 E V D V F V S M G Y H K K T Y 14 111 R V F L K G G
S D S D A S L V 14 123 S L V I T D L T L E D Y G R Y 14 126 I T D L
T L E D Y G R Y K C E 14 128 D L T L E D Y G R Y K C E V I 14 138 K
C E V I E G L E D D T V V V 14 147 D D T V V V A L D L Q G V V F 14
153 A L D L Q G V V F P Y F P R L 14 156 L Q G V V F P Y F P R L G
R Y 14 169 R Y N L N F H E A Q Q A C L D 14 199 R G G L D W C N A G
W L S D G 14 212 D G S V Q Y P I T K P R E P C 14 232 V P G V R N Y
G F W D K D K S 14 289 V G Q I F A A W K I L G Y D R 14 296 W K I L
G Y D R C D A G W L A 14 311 D G S V R Y P I S R P R R R C 14 332 V
R F V G F P D K K H K L Y G 14 10 I S I C W A D H L S D N Y T L 12
12 I C W A D H L S D N Y T L D H 12 13 C W A D H L S D N Y T L D H
D 12 25 D H D R A I H I Q A E N G P H 12 28 R A I H I Q A E N G P H
L L V 12 31 H I Q A E N G P H L L V E A E 12 35 E N G P H L L V E A
E Q A K V 12 36 N G P H L L V E A E Q A K V F 12 43 E A E Q A K V F
S H R G G N V 12 44 A E Q A K V F S H R G G N V T 12 45 E Q A K V F
S H R G G N V T L 12 48 K V F S H R G G N V T L P C K 12 51 S H R G
G N V T L P C K F Y R 12 63 F Y R D P T A F G S G I H K I 12 64 Y R
D P T A F G S G I H K I R 12 68 T A F G S G I H K I R I K W T 12 73
G I H K I R I K W T K L T S D 12 83 K L T S D Y L K E V D V F V S
12 87 D Y L K E V D V F V S M G Y H 12 101 H K K T Y G G Y Q G R V
F L K 12 103 K T Y G G Y Q G R V F L K G G 12 107 G Y Q G R V F L K
G G S D S D 12 112 V F L K G G S D S D A S L V I 12 113 F L K G G S
D S D A S L V I T 12 116 G G S D S D A S L V I T D L T 12 118 S D S
D A S L V I T D L T L E 12 120 S D A S L V I T D L T L E D Y 12 127
T D L T L E D Y G R Y K C E V 12 140 E V I E G L E D D T V V V A L
12 145 L E D D T V V V A L D L Q G V 12 146 E D D T V V V A L D L Q
G V V 12 166 R L G R Y N L N F H E A Q Q A 12 168 G R Y N L N F H E
A Q Q A C L 12 170 Y N L N F H E A Q Q A C L D Q 12 177 A Q Q A C L
D Q D A V I A S F 12 183 D Q D A V I A S F D Q L Y D A 12 186 A V I
A S F D Q L Y D A W R G 12 196 D A W R G G L D W C N A G W L 12 203
D W C N A G W L S D G S V Q Y 12 204 W C N A G W L S D G S V Q Y P
12 208 G W L S D G S V Q Y P I T K P 12 209 W L S D G S V Q Y P I T
K P R 12 218 P I T K P R E P C G G Q N T V 12 221 K P R E P C G G Q
N T V P G V 12 226 C G G Q N T V P G V R N Y G F 12 234 G V R N Y G
F W D K D K S R Y 12 243 K D K S R Y D V F C F T S N F 12 244 D K S
R Y D V F C F T S N F N 12 264 L I H P T K L T Y D E A V Q A 12 270
L T Y D E A V Q A C L N D G A 12 274 E A V Q A C L N D G A Q I A K
12 276 V Q A C L N D G A Q I A K V G 12 278 A C L N D G A Q I A K V
G Q I 12 280 L N D G A Q I A K V G Q I F A 12 281 N D G A Q I A K V
G Q I F A A 12 287 A K V G Q I F A A W K I L G Y 12 288 K V G Q I F
A A W K I L G Y D 12 299 L G Y D R C D A G W L A D G S 12 303 R C D
A G W L A D G S V R Y P 12 307 G W L A D G S V R Y P I S R P 12 308
W L A D G S V R Y P I S R P R 12 312 G S V R Y P I S R P R R R C S
12 320 R P R R R C S P T E A A V R F 12 324 R C S P T E A A V R F V
G F P 12 325 C S P T E A A V R F V G F P D 12 333 R F V G F P D K K
H K L Y G V 12 47 A K V F S H R G G N V T L P C 11 160 V F P Y F P
R L G R Y N L N F 11 254 T S N F N G R F Y Y L I H P T 11 334 F V G
F P D K K H K L Y G V Y 11 102 K K T Y G G Y Q G R V F L K G 10 192
D Q L Y D A W R G G L D W C N 10 214 S V Q Y P I T K P R E P C G G
10 290 G Q I F A A W K I L G Y D R C 10 313 S V R Y P I S R P R R R
C S P 10 109 Q G R V F L K G G S D S D A S 9 5 L L L V L I S I C W
A D H L S 8 27 D R A I H I Q A E N G P H L L 8 54 G G N V T L P C K
F Y R D P T 8 76 K I R I K W T K L T S D Y L K 8 95 F V S M G Y H K
K T Y G G Y Q 8 121 D A S L V I T D L T L E D Y G 8 151 V V A L D L
Q G V V F P Y F P 8 157 Q G V V F P Y F P R L G R Y N 8 164 F P R L
G R Y N L N F H E A Q 8 184 Q D A V I A S F D Q L Y D A W 8 207 A G
W L S D G S V Q Y P I T K 8 216 Q Y P I T K P R E P C G G Q N 8 261
F Y Y L I H P T K L T Y D E A 8 262 Y Y L I H P T K L T Y D E A V 8
306 A G W L A D G S V R Y P I S R 8 239 G F W D K D K S R Y D V F C
F 7 8 V L I S I C W A D H L S D N Y 6 14 W A D H L S D N Y T L D H
D R 6 20 D N Y T L D H D R A I H I Q A 6 24 L D H D R A I H I Q A E
N G P 6 26 H D R A I H I Q A E N G P H L 6 30 I H I Q A E N G P H L
L V E A 6 33 Q A E N G P H L L V E A E Q A 6 34 A E N G P H L L V E
A E Q A K 6 40 L L V E A E Q A K V F S H R G 6 41 L V E A E Q A K V
F S H R G G 6 50 F S H R G G N V T L P C K F Y 6 53 R G G N V T L P
C K F Y R D P 6 58 T L P C K F Y R D P T A F G S 6 65 R D P T A F G
S G I H K I R I 6 66 D P T A F G S G I H K I R I K 6 69 A F G S G I
H K I R I K W T K 6 75 H K I R I K W T K L T S D Y L 6 79 I K W T K
L T S D Y L K E V D 6 88 Y L K E V D V F V S M G Y H K 6 90 K E V D
V F V S M G Y H K K T 6 98 M G Y H K K T Y G G Y Q G R V 6 104 T Y
G G Y Q G R V F L K G G S 6 106 G G Y Q G R V F L K G G S D S 6 108
Y Q G R V F L K G G S D S D A 6 114 L K G G S D S D A S L V I T D 6
125 V I T D L T L E D Y G R Y K C 6 135 G R Y K C E V I E G L E D D
T 6 136 R Y K C E V I E G L E D D T V 6 137 Y K C E V I E G L E D D
T V V 6 143 E G L E D D T V V V A L D L Q 6 144 G L E D D T V V V A
L D L Q G 6 150 V V V A L D L Q G V V F P Y F 6 154 L D L Q G V V F
P Y F P R L G 6 155 D L Q G V V F P Y F P R L G R 6 162 P Y F P R L
G R Y N L N F H E 6 165 P R L G R Y N L N F H E A Q Q 6 173 N F H E
A Q Q A C L D Q D A V 6 174 F H E A Q Q A C L D Q D A V I 6 175 H E
A Q Q A C L D Q D A V I A 6 178 Q Q A C L D Q D A V I A S F D 6 180
A C L D Q D A V I A S F D Q L 6 181 C L D Q D A V I A S F D Q L Y 6
190 S F D Q L Y D A W R G G L D W 6 197 A W R G G L D W C N A G W L
S 6 198 W R G G L D W C N A G W L S D 6 200 G G L D W C N A G W L S
D G S 6 205 C N A G W L S D G S V Q Y P I 6 210 L S D G S V Q Y P I
T K P R E 6 213 G S V Q Y P I T K P R E P C G 6 219 I T K P R E P C
G G Q N T V P 6 220 T K P R E P C G G Q N T V P G 6 222 P R E P C G
G Q N T V P G V R 6 223 R E P C G G Q N T V P G V R N 6 224 E P C G
G Q N T V P G V R N Y 6 228 G Q N T V P G V R N Y G F W D 6 236 R N
Y G F W D K D K S R Y D V 6 246 S R Y D V F C F T S N F N G R 6 251
F C F T S N F N G R F Y Y L I 6 252 C F T S N F N G R F Y Y L I H 6
253 F T S N F N G R F Y Y L I H P 6 255 S N F N G R F Y Y L I H P T
K 6 257 F N G R F Y Y L I H P T K L T 6 265 I H P T K L T Y D E A V
Q A C 6 266 H P T K L T Y D E A V Q A C L 6 268 T K L T Y D E A V Q
A C L N D 6 272 Y D E A V Q A C L N D G A Q I 6 275 A V Q A C L N D
G A Q I A K V 6 284 A Q I A K V G Q I F A A W K I 6 292 I F A A W K
I L G Y D R C D A 6 300 G Y D R C D A G W L A D G S V 6 302 D R C D
A G W L A D G S V R Y 6 304 C D A G W L A D G S V R Y P I 6 319 S R
P R R R C S P T E A A V R 6 321 P R R R C S P T E A A V R F V 6 323
R R C S P T E A A V R F V G F 6 326 S P T E A A V R F V G F P D K 6
328 T E A A V R F V G F P D K K H 6 330 A A V R F V G F P D K K H K
L 6 336 G F P D K K H K L Y G V Y C F 6 338 P D K K H K L Y G V Y C
F R A 6 97 S M G Y H K K T Y G G Y Q G R 5 105 Y G G Y Q G R V F L
K G G S D 5 237 N Y G F W D K D K S R Y D V F 5 56 N V T L P C K F
Y R D P T A F 3 22 Y T L D H D R A I H I Q A E N 1 70 F G S G I H K
I R I K W T K L 1 72 S G I H K I R I K W T K L T S 1 77 I R I K W T
K L T S D Y L K E 1 96 V S M G Y H K K T Y G G Y Q G 1 130 T L E D
Y G R Y K C E V I E G 1 163 Y F P R L G R Y N L N F H E A 1 215 V Q
Y P I T K P R E P C G G Q 1 263 Y L I H P T K L T Y D E A V Q 1 314
V R Y P I S R P R R R C S P T 1 316 Y P I S R P R R R C S P T E A 1
317 P I S R P R R R C S P T E A A 1 318 I S R P R R R C S P T E A A
V 1 42 V E A E Q A K V F S H R G G N -5 59 L P C K F Y R D P T A F
G S G -5 84 L T S D Y L K E V D V F V S M -5 132 E D Y G R Y K C E
V I E G L E -5 193 Q L Y D A W R G G L D W C N A -5 217 Y P I T K P
R E P C G G Q N T -5 230 N T V P G V R N Y G F W D K D -5 241 W D K
D K S R Y D V F C F T S -5 282 D G A Q I A K V G Q I F A A W -5 291
Q I F A A W K I L G Y D R C D -5 297 K I L G Y D R C D A G W L A D
-5 309 L A D G S V R Y P I S R P R R -5 327 P T E A A V R F V G F P
D K K -5 335 V G F P D K K H K L Y G V Y C -5 337 F P D K K H K L Y
G V Y C F R -5 151P3D4 v.2: HLA Peptide Scoring Results DRB1*0401
15 - mers SYFPEITHI 111 K L K Y L A F L H K R M N T N 28 281 P A A
W L P L R T P W T R P S 28 40 P T K V T G I I T Q G A K D F 26 54 F
G H V Q F V G S Y K L A Y S 26 51 A K D F G H V Q F V G S Y K L 22
60 V G S Y K L A Y S N D G E H W 22 64 K L A Y S N D G E H W T V Y
Q 22 74 W T V Y Q D E K Q R K D K V L 22 158 S E A Y K K V C L S G
A P H E 22 233 G F I F K T I A P L A A T R A 22 288 R T P W T R P S
S C P T S S S 22 357 N N S W Y V E N G R P A D L A 22 372 G S G Y C
G A L W K A I E S L 22 377 G A L W K A I E S L E E G L G 22 14 L H
I V V E S I R D H S G Q K 20 26 G Q K M K Q D K K V D L L V P 20 32
D K K V D L L V P T K V T G I 20 73 H W T V Y Q D E K Q R K D K V
20 93 A V V V S C E G I N I S G S F 20 109 R N K L K Y L A F L H K
R M N 20 112 L K Y L A F L H K R M N T N P 20 163 K V C L S G A P H
E V G W K Y 20 200 K Q L M R L Q K Q A E K N M K 20 229 P R G L G F
I F K T I A P L A 20 236 F K T I A P L A A T R A T R I 20 284 W L P
L R T P W T R P S S C P 20 313 R N P L P N P R H S P S G G G 20 326
G G G L K K P A R H C Q G Q K 20 7 K T F P L R A L H I V V E S I 18
17 V V E S I R D H S G Q K M K Q 18 33 K K V D L L V P T K V T G I
I 18 41 T K V T G I I T Q G A K D F G 18 70 D G E H W T V Y Q D E K
Q R K 18 83 R K D K V L L G R K A V V V S 18 101 I N I S G S F C R
N K L K Y L 18 134 Q V P S R I F W R Q E K A D G 18 173 V G W K Y Q
A V T A T L E E K 18 180 V T A T L E E K R K E K A E I 18 187 K R K
E K A E I H Y R K N K Q 18 196 Y R K N K Q L M R L Q K Q A E 18 204
R L Q K Q A E K N M K K K I D 18 237 K T I A P L A A T R A T R I G
18 258 P R A G S S A H R P P A L S A 18 263 S A H R P P A L S A R A
P V P 18 272 A R A P V P A A S P A A W L P 18 71 G E H W T V Y Q D
E K Q R K D 16 104 S G S F C R N K L K Y L A F L 16 128 R R P Y H F
Q V P S R I F W R 16 130 P Y H F Q V P S R I F W R Q E 16 138 R I F
W R Q E K A D G G S C C 16 172 E V G W K Y Q A V T A T L E E 16 174
G W K Y Q A V T A T L E E K R 16 193 E I H Y R K N K Q L M R L Q K
16 217 I D K Y T E S P G G G S P R G 16 301 S S T Y D S L S P Y G P
R N P 16 358 N S W Y V E N G R P A D L A G 16 36 D L L V P T K V T
G I I T Q G 15 170 P H E V G W K Y Q A V T A T L 15 191 K A E I H Y
R K N K Q L M R L 15 8 T F P L R A L H I V V E S I R 14 11 L R A L
H I V V E S I R D H S 14 13 A L H I V V E S I R D H S G Q 14 15 H I
V V E S I R D H S G Q K M 14 18 V E S I R D H S G Q K M K Q D 14 35
V D L L V P T K V T G I I T Q 14 57 V Q F V G S Y K L A Y S N D G
14 84 K D K V L L G R K A V V V S C 14 91 R K A V V V S C E G I N I
S G 14 92 K A V V V S C E G I N I S G S 14 98 C E G I N I S G S F C
R N K L 14 100 G I N I S G S F C R N K L K Y 14 119 H K R M N T N P
S R R P Y H F 14 199 N K Q L M R L Q K Q A E K N M 14 202 L M R L Q
K Q A E K N M K K K 14 232 L G F I F K T I A P L A A T R 14 239 I A
P L A A T R A T R I G H P 14 273 R A P V P A A S P A A W L P L 14
341 H N V L A R G K P Q R K P K S 14 359 S W Y V E N G R P A D L A
G S 14 367 P A D L A G S G Y C G A L W K 14 376 C G A L W K A I E S
L E E G L 14 380 W K A I E S L E E G L G G K Q 14 383 I E S L E E G
L G G K Q K D K 14 3 E H T T K T F P L R A L H I V 12 5 T T K T F P
L R A L H I V V E 12 10 P L R A L H I V V E S I R D H 12 12 R A L H
I V V E S I R D H S G 12 19 E S I R D H S G Q K M K Q D K 12 23 D H
S G Q K M K Q D K K V D L 12 30 K Q D K K V D L L V P T K V T 12 31
Q D K K V D L L V P T K V T G 12 37 L L V P T K V T G I I T Q G A
12 47 I T Q G A K D F G H V Q F V G 12 48 T Q G A K D F G H V Q F V
G S 12 53 D F G H V Q F V G S Y K L A Y 12 65 L A Y S N D G E H W T
V Y Q D 12 67 Y S N D G E H W T V Y Q D E K 12 81 K Q R K D K V L L
G R K A V V 12 82 Q R K D K V L L G R K A V V V 12 89 L G R K A V V
V S C E G I N I 12 90 G R K A V V V S C E G I N I S 12 95 V V S C E
G I N I S G S F C R 12 102 N I S G S F C R N K L K Y L A 12 113 K Y
L A F L H K R M N T N P S 12 116 A F L H K R M N T N P S R R P 12
124 T N P S R R P Y H F Q V P S R 12 126 P S R R P Y H F Q V P S R
I F 12 129 R P Y H F Q V P S R I F W R Q 12 135 V P S R I F W R Q E
K A D G G 12 146 A D G G S C C P Q G H A S E A 12 151 C C P Q G H A
S E A Y K K V C 12 153 P Q G H A S E A Y K K V C L S 12 167 S G A P
H E V G W K Y Q A V T 12 176 K Y Q A V T A T L E E K R K E 12 178 Q
A V T A T L E E K R K E K A 12 188 R K E K A E I H Y R K N K Q L 12
189 K E K A E I H Y R K N K Q L M 12 203 M R L Q K Q A E K N M K K
K I 12 212 N M K K K I D K Y T E S P G G 12 226 G G S P R G L G F I
F K T
I A 12 228 S P R G L G F I F K T I A P L 12 230 R G L G F I F K T I
A P L A A 12 234 F I F K T I A P L A A T R A T 12 238 T I A P L A A
T R A T R I G H 12 241 P L A A T R A T R I G H P G G 12 244 A T R A
T R I G H P G G R T P 12 249 R I G H P G G R T P R A G S S 12 251 G
H P G G R T P R A G S S A H 12 254 G G R T P R A G S S A H R P P 12
265 H R P P A L S A R A P V P A A 12 268 P A L S A R A P V P A A S
P A 12 276 V P A A S P A A W L P L R T P 12 285 L P L R T P W T R P
S S C P T 12 291 W T R P S S C P T S S S T Y D 12 292 T R P S S C P
T S S S T Y D S 12 295 S S C P T S S S T Y D S L S P 12 305 D S L S
P Y G P R N P L P N P 12 310 Y G P R N P L P N P R H S P S 12 327 G
G L K K P A R H C Q G Q K H 12 329 L K K P A R H C Q G Q K H N V 12
331 K P A R H C Q G Q K H N V L A 12 333 A R H C Q G Q K H N V L A
R G 12 337 Q G Q K H N V L A R G K P Q R 12 338 G Q K H N V L A R G
K P Q R K 12 339 Q K H N V L A R G K P Q R K P 12 343 V L A R G K P
Q R K P K S E N 12 347 G K P Q R K P K S E N N S W Y 12 350 Q R K P
K S E N N S W Y V E N 12 351 R K P K S E N N S W Y V E N G 12 356 E
N N S W Y V E N G R P A D L 12 362 V E N G R P A D L A G S G Y C 12
365 G R P A D L A G S G Y C G A L 12 382 A I E S L E E G L G G K Q
K D 12 384 K S L E E G L G G K Q K D K E 12 386 L E E G L G G K Q K
D K E R K 12 390 L G G K Q K D K E R K A E N G 12 392 G K Q K D K E
R K A E N G P H 12 395 K D K E R K A E N G P H L L V 12 396 D K E R
K A E N G P H L L V E 12 398 E R K A E N G P H L L V E A E 12 6 T K
T F P L R A L H I V V E S 11 114 Y L A F L H K R M N T N P S R 11
231 G L G F I F K T I A P L A A T 11 307 L S P Y G P R N P L P N P
R H 11 56 H V Q F V G S Y K L A Y S N D 10 137 S R I F W R Q E K A
D G G S C 10 85 D K V L L G R K A V V V S C E 9 86 K V L L G R K A
V V V S C E G 9 115 L A F L H K R M N T N P S R R 9 132 H F Q V P S
R I F W R Q E K A 9 181 T A T L E E K R K E K A E I H 9 210 E K N M
K K K I D K Y T E S P 9 267 P P A L S A R A P V P A A S P 9 34 K V
D L L V P T K V T G I I T 8 43 V T G I I T Q G A K D F G H V 8 44 T
G I I T Q G A K D F G H V Q 8 62 S Y K L A Y S N D G E H W T V 8
161 Y K K V C L S G A P H E V G W 8 177 Y Q A V T A T L E E K R K E
K 8 214 K K K I D K Y T E S P G G G S 8 247 A T R I G H P G G R T P
R A G 8 304 Y D S L S P Y G P R N P L P N 8 16 I V V E S I R D H S
G Q K M K 7 75 T V Y Q D E K Q R K D K V L L 7 198 K N K Q L M R L
Q K Q A E K N 7 334 R H C Q G Q K H N V L A R G K 7 2 L E H T T K T
F P L R A L H I 6 4 H T T K T F P L R A L H I V V 6 9 F P L R A L H
I V V E S I R D 6 20 S I R D H S G Q K M K Q D K K 6 29 M K Q D K K
V D L L V P T K V 6 38 L V P T K V T G I I T Q G A K 6 45 G I I T Q
G A K D F G H V Q F 6 49 Q G A K D F G H V Q F V G S Y 6 50 G A K D
F G H V Q F V G S Y K 6 55 G H V Q F V G S Y K L A Y S N 6 59 F V G
S Y K L A Y S N D G E H 6 61 G S Y K L A Y S N D G E H W T 6 66 A Y
S N D G E H W T V Y Q D E 6 76 V Y Q D E K Q R K D K V L L G 6 79 D
E K Q R K D K V L L G R K A 6 87 V L L G R K A V V V S C E G I 6 88
L L G R K A V V V S C E G I N 6 94 V V V S C E G I N I S G S F C 6
96 V S C E G I N I S G S F C R N 6 97 S C E G I N I S G S F C R N K
6 99 E G I N I S G S F C R N K L K 6 106 S F C R N K L K Y L A F L
H K 6 110 N K L K Y L A F L H K R M N T 6 117 F L H K R M N T N P S
R R P Y 6 120 K R M N T N P S R R P Y H F Q 6 121 R M N T N P S R R
P Y H F Q V 6 127 S R R P Y H F Q V P S R I F W 6 133 F Q V P S R I
F W R Q E K A D 6 140 F W R Q E K A D G G S C C P Q 6 141 W R Q E K
A D G G S C C P Q G 6 142 R Q E K A D G G S C C P Q G H 6 143 Q E K
A D G G S C C P Q G H A 6 147 D G G S C C P Q G H A S E A Y 6 148 G
G S C C P Q G H A S E A Y K 6 149 G S C C P Q G H A S E A Y K K 6
150 S C C P Q G H A S E A Y K K V 6 152 C P Q G H A S E A Y K K V C
L 6 154 Q G H A S E A Y K K V C L S G 6 155 G H A S E A Y K K V C L
S G A 6 159 E A Y K K V C L S G A P H E V 6 160 A Y K K V C L S G A
P H E V G 6 162 K K V C L S G A P H E V G W K 6 165 C L S G A P H E
V G W K Y Q A 6 166 L S G A P H E V G W K Y Q A V 6 168 G A P H E V
G W K Y Q A V T A 6 169 A P H E V G W K Y Q A V T A T 6 171 H E V G
W K Y Q A V T A T L E 6 175 W K Y Q A V T A T L E E K R K 6 179 A V
T A T L E E K R K E K A E 6 184 L E E K R K E K A E I H Y R K 6 186
E K R K E K A E I H Y R K N K 6 190 E K A E I H Y R K N K Q L M R 6
195 H Y R K N K Q L M R L Q K Q A 6 197 R K N K Q L M R L Q K Q A E
K 6 206 Q K Q A E K N M K K K I D K Y 6 211 K N M K K K I D K Y T E
S P G 6 215 K K I D K Y T E S P G G G S P 6 216 K I D K Y T E S P G
G G S P R 6 220 Y T E S P G G G S P R G L G F 6 221 T E S P G G G S
P R G L G F I 6 222 E S P G G G S P R G L G F I F 6 227 G S P R G L
G F I F K T I A P 6 246 R A T R I G H P G G R T P R A 6 248 T R I G
H P G G R T P R A G S 6 252 H P G G R T P R A G S S A H R 6 255 G R
T P R A G S S A H R P P A 6 257 T P R A G S S A H R P P A L S 6 259
R A G S S A H R P P A L S A R 6 261 G S S A H R P P A L S A R A P 6
264 A H R P P A L S A R A P V P A 6 266 R P P A L S A R A P V P A A
S 6 269 A L S A R A P V P A A S P A A 6 270 L S A R A P V P A A S P
A A W 6 271 S A R A P V P A A S P A A W L 6 274 A P V P A A S P A A
W L P L R 6 277 P A A S P A A W L P L R T P W 6 278 A A S P A A W L
P L R T P W T 6 279 A S P A A W L P L R T P W T R 6 280 S P A A W L
P L R T P W T R P 6 289 T P W T R P S S C P T S S S T 6 290 P W T R
P S S C P T S S S T Y 6 293 R P S S C P T S S S T Y D S L 6 294 P S
S C P T S S S T Y D S L S 6 296 S C P T S S S T Y D S L S P Y 6 297
C P T S S S T Y D S L S P Y G 6 298 P T S S S T Y D S L S P Y G P 6
299 T S S S T Y D S L S P Y G P R 6 300 S S S T Y D S L S P Y G P R
N 6 303 T Y D S L S P Y G P R N P L P 6 306 S L S P Y G P R N P L P
N P R 6 311 G P R N P L P N P R H S P S G 6 312 P R N P L P N P R H
S P S G G 6 316 L P N P R H S P S G G G G L K 6 318 N P R H S P S G
G G G L K K P 6 319 P R H S P S G G G G L K K P A 6 320 R H S P S G
G G G L K K P A R 6 322 S P S G G G G L K K P A R H C 6 323 P S G G
G G L K K P A R H C Q 6 332 P A R H C Q G Q K H N V L A R 6 344 L A
R G K P Q R K P K S E N N 6 349 P Q R K P K S E N N S W Y V E 6 353
P K S E N N S W Y V E N G R P 6 363 E N G R P A D L A G S G Y C G 6
364 N G R P A D L A G S G Y C G A 6 368 A D L A G S G Y C G A L W K
A 6 370 L A G S G Y C G A L W K A I E 6 371 A G S G Y C G A L W K A
I E S 6 373 S G Y C G A L W K A I E S L E 6 374 G Y C G A L W K A I
E S L E E 6 378 A L W K A I E S L E E G L G G 6 379 L W K A I E S L
E E G L G G K 6 381 K A I E S L E E G L G G K Q K 6 397 K E R K A E
N G P H L L V E A 6 400 K A E N G P H L L V E A E Q A 6 136 P S R I
F W R Q E K A D G G S 3 282 A A W L P L R T P W T R P S S 3 340 K H
N V L A R G K P Q R K P K 3 387 E E G L G G K Q K D K E R K A 3 22
R D H S G Q K M K Q D K K V D 1 24 H S G Q K M K Q D K K V D L L 1
27 Q K M K Q D K K V D L L V P T 1 28 K M K Q D K K V D L L V P T K
1 46 I I T Q G A K D F G H V Q F V 1 58 Q F V G S Y K L A Y S N D G
E 1 77 Y Q D E K Q R K D K V L L G R 1 78 Q D E K Q R K D K V L L G
R K 1 105 G S F C R N K L K Y L A F L H 1 107 F C R N K L K Y L A F
L H K R 1 123 N T N P S R R P Y H F Q V P S 1 139 I F W R Q E K A D
G G S C C P 1 156 H A S E A Y K K V C L S G A P 1 183 T L E E K R K
E K A E I H Y R 1 192 A E I H Y R K N K Q L M R L Q 1 194 I H Y R K
N K Q L M R L Q K Q 1 201 Q L M R L Q K Q A E K N M K K 1 205 L Q K
Q A E K N M K K K I D K 1 208 Q A E K N M K K K I D K Y T E 1 213 M
K K K I D K Y T E S P G G G 1 224 P G G G S P R G L G F I F K T 1
240 A P L A A T R A T R I G H P G 1 253 P G G R T P R A G S S A H R
P 1 260 A G S S A H R P P A L S A R A 1 287 L R T P W T R P S S C P
T S S 1 314 N P L P N P R H S P S G G G G 1 328 G L K K P A R H C Q
G Q K H N 1 342 N V L A R G K P Q R K P K S E 1 346 R G K P Q R K P
K S E N N S W 1 348 K P Q R K P K S E N N S W Y V 1 360 W Y V E N G
R P A D L A G S G 1 375 Y C G A L W K A I E S L E E G 1 389 G L G G
K Q K D K E R K A E N 1 391 G G K Q K D K E R K A E N G P 1 1 M L E
H T T K T F P L R A L H -5 80 E K Q R K D K V L L G R K A V -5 103
I S G S F C R N K L K Y L A F -5 122 M N T N P S R R P Y H F Q V P
-5 157 A S E A Y K K V C L S G A P H -5 182 A T L E E K R K E K A E
I H Y -5 185 E E K R K E K A E I H Y R K N -5 209 A E K N M K K K I
D K Y T E S -5 243 A A T R A T R I G H P G G R T -5 250 I G H P G G
R T P R A G S S A -5 324 S G G G G L K K P A R H C Q G -5 325 G G G
G L K K P A R H C Q G Q -5 345 A R G K P Q R K P K S E N N S -5 393
K Q K D K E R K A E N G P H L -5 394 Q K D K E R K A E N G P H L L
-5
[0851]
58TABLE LI SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 score NO.
151P3D4 v.1: HLA Peptide Scoring Results DRB1*1101 15-mers
SYFPEITHI 235 V R N Y G F W D K D K S R Y D 25 161 F P Y F P R L G
R Y N L N F H 24 258 N G R F Y Y L I H P T K L T Y 24 18 L S D N Y
T L D H D R A I H I 22 289 V G Q I F A A W K I L G Y D R 22 315 R Y
P I S R P R R R C S P T E 21 95 F V S M G Y H K K T Y G G Y Q 20
237 N Y G F W D K D K S R Y D V F 20 295 A W K I L G Y D R C D A G
W L 20 67 P T A F G S G I H K I R I K W 19 86 S D Y L K E V D V F V
S M G Y 19 105 Y G G Y Q G R V F L K G G S D 19 334 F V G F P D K K
H K L Y G V Y 19 4 L L L L V L I S I C W A D H L 18 78 R I K W T K
L T S D Y L K E V 18 158 G V V F P Y F P R L G R Y N L 18 167 L G R
Y N L N F H E A Q Q A C 18 283 G A Q I A K V G Q I F A A W K 18 293
F A A W K I L G Y D R C D A G 18 92 V D V F V S M G Y H K K T Y G
17 214 S V Q Y P I T K P R E P C G G 17 259 G R F Y Y L I H P T K L
T Y D 17 325 C S P T E A A V R F V G F P D 17 44 A E Q A K V F S H
R G G N V T 16 54 G G N V T L P C K F Y R D P T 16 60 P C K F Y R D
P T A F G S G I 16 61 C K F Y R D P T A F G S G I H 16 68 T A F G S
G I H K I R I K W T 16 188 I A S F D Q L Y D A W R G G L 16 213 G S
V Q Y P I T K P R E P C G 16 228 G Q N T V P G V R N Y G F W D 16
248 Y D V F C F T S N F N G R F Y 16 312 G S V R Y P I S R P R R R
C S 16 93 D V F V S M G Y H K K T Y G G 15 107 G Y Q G R V F L K G
G S D S D 15 128 D L T L E D Y G R Y K C E V I 15 157 Q G V V F P Y
F P R L G R Y N 15 1 M K S L L L L V L I S I C W A 14 9 L I S I C W
A D H L S D N Y T 14 23 T L D H D R A I H I Q A E N G 14 40 L L V E
A E Q A K V F S H R G 14 43 E A E Q A K V F S H R G G N V 14 75 H K
I R I K W T K L T S D Y L 14 123 S L V I T D L T L E D Y G R Y 14
153 A L D L Q G V V F P Y F P R L 14 191 F D Q L Y D A W R G G L D
W C 14 216 Q Y P I T K P R E P C G G Q N 14 250 V F C F T S N F N G
R F Y Y L 14 261 F Y Y L I H P T K L T Y D E A 14 264 L I H P T K L
T Y D E A V Q A 14 267 P T K L T Y D E A V Q A C L N 14 280 L N D G
A Q I A K V G Q I F A 14 316 Y P I S R P R R R C S P T E A 14 332 V
R F V G F P D K K H K L Y G 14 335 V G F P D K K H K L Y G V Y C 14
2 K S L L L L V L I S I C W A D 13 3 S L L L L V L I S I C W A D H
13 19 S D N Y T L D H D R A I H I Q 13 56 N V T L P C K F Y R D P T
A F 13 109 Q G R V F L K G G S D S D A S 13 142 I E G L E D D T V V
V A L D L 13 147 D D T V V V A L D L Q G V V F 13 154 L D L Q G V V
F P Y F P R L G 13 306 A G W L A D G S V R Y P I S R 13 308 W L A D
G S V R Y P I S R P R 13 313 S V R Y P I S R P R R R C S P 13 6 L L
V L I S I C W A D H L S D 12 26 H D R A I H I Q A E N G P H L 12 27
D R A I H I Q A E N G P H L L 12 36 N G P H L L V E A E Q A K V F
12 71 G S G I H K I R I K W T K L T 12 85 T S D Y L K E V D V F V S
M G 12 88 Y L K E V D V F V S M G Y H K 12 102 K K T Y G G Y Q G R
V F L K G 12 106 G G Y Q G R V F L K G G S D S 12 111 R V F L K G G
S D S D A S L V 12 134 Y G R Y K C E V I E G L E D D 12 139 C E V I
E G L E D D T V V V A 12 148 D T V V V A L D L Q G V V F P 12 151 V
V A L D L Q G V V F P Y F P 12 160 V F P Y F P R L G R Y N L N F 12
166 R L G R Y N L N F H E A Q Q A 12 169 R Y N L N F H E A Q Q A C
L D 12 179 Q A C L D Q D A V I A S F D Q 12 196 D A W R G G L D W C
N A G W L 12 207 A G W L S D G S V Q Y P I T K 12 229 Q N T V P G V
R N Y G F W D K 12 244 D K S R Y D V F C F T S N F N 12 269 K L T Y
D E A V Q A C L N D G 12 273 D E A V Q A C L N D G A Q I A 12 286 I
A K V G Q I F A A W K I L G 12 296 W K I L G Y D R C D A G W L A 12
305 D A G W L A D G S V R Y P I S 12 329 E A A V R F V G F P D K K
H K 12 47 A K V F S H R G G N V T L P C 11 131 L E D Y G R Y K C E
V I E G L 11 145 L E D D T V V V A L D L Q G V 11 192 D Q L Y D A W
R G G L D W C N 11 238 Y G F W D K D K S R Y D V F C 11 245 K S R Y
D V F C F T S N F N G 11 254 T S N F N G R F Y Y L I H P T 11 260 R
F Y Y L I H P T K L T Y D E 11 314 V R Y P I S R P R R R C S P T 11
331 A V R F V G F P D K K H K L Y 11 11 S I C W A D H L S D N Y T L
D 10 97 S M G Y H K K T Y G G Y Q G R 10 110 G R V F L K G G S D S
D A S L 10 126 I T D L T L E D Y G R Y K C E 10 171 N L N F H E A Q
Q A C L D Q D 10 195 Y D A W R G G L D W C N A G W 10 201 G L D W C
N A G W L S D G S V 10 206 N A G W L S D G S V Q Y P I T 10 290 G Q
I F A A W K I L G Y D R C 10 298 I L G Y D R C D A G W L A D G 10
307 G W L A D G S V R Y P I S R P 10 333 R F V G F P D K K H K L Y
G V 10 20 D N Y T L D H D R A I H I Q A 9 31 H I Q A E N G P H L L
V E A E 9 70 F G S G I H K I R I K W T K L 9 82 T K L T S D Y L K E
V D V F V 9 89 L K E V D V F V S M G Y H K K 9 144 G L E D D T V V
V A L D L Q G 9 35 E N G P H L L V E A E Q A K V 8 45 E Q A K V F S
H R G G N V T L 8 57 V T L P C K F Y R D P T A F G 8 72 S G I H K I
R I K W T K L T S 8 81 W T K L T S D Y L K E V D V F 8 91 E V D V F
V S M G Y H K K T Y 8 94 V F V S M G Y H K K T Y G G Y 8 103 K T Y
G G Y Q G R V F L K G G 8 118 S D S D A S L V I T D L T L E 8 130 T
L E D Y G R Y K C E V I E G 8 146 E D D T V V V A L D L Q G V V 8
156 L Q G V V F P Y F P R L G R Y 8 189 A S F D Q L Y D A W R G G L
D 8 215 V Q Y P I T K P R E P C G G Q 8 226 C G G Q N T V P G V R N
Y G F 8 239 G F W D K D K S R Y D V F C F 8 252 C F T S N F N G R F
Y Y L I H 8 310 A D G S V R Y P I S R P R R R 8 8 V L I S I C W A D
H L S D N Y 7 37 G P H L L V E A E Q A K V F S 7 38 P H L L V E A E
Q A K V F S H 7 39 H L L V E A E Q A K V F S H R 7 46 Q A K V F S H
R G G N V T L P 7 49 V F S H R G G N V T L P C K F 7 73 G I H K I R
I K W T K L T S D 7 74 I H K I R I K W T K L T S D Y 7 119 D S D A
S L V I T D L T L E D 7 120 S D A S L V I T D L T L E D Y 7 121 D A
S L V I T D L T L E D Y G 7 135 G R Y K C E V I E G L E D D T 7 136
R Y K C E V I E G L E D D T V 7 149 T V V V A L D L Q G V V F P Y 7
150 V V V A L D L Q G V V F P Y F 7 178 Q Q A C L D Q D A V I A S F
D 7 182 L D Q D A V I A S F D Q L Y D 7 184 Q D A V I A S F D Q L Y
D A W 7 190 S F D Q L Y D A W R G G L D W 7 200 G G L D W C N A G W
L S D G S 7 209 W L S D G S V Q Y P I T K P R 7 211 S D G S V Q Y P
I T K P R E P 7 222 P R E P C G G Q N T V P G V R 7 247 R Y D V F C
F T S N F N G R F 7 270 L T Y D E A V Q A C L N D G A 7 276 V Q A C
L N D G A Q I A K V G 7 279 C L N D G A Q I A K V G Q I F 7 284 A Q
I A K V G Q I F A A W K I 7 299 L G Y D R C D A G W L A D G S 7 311
D G S V R Y P I S R P R R R C 7 327 P T E A A V R F V G F P D K K 7
5 L L L V L I S I C W A D H L S 6 7 L V L I S I C W A D H L S D N 6
12 I C W A D H L S D N Y T L D H 6 15 A D H L S D N Y T L D H D R A
6 21 N Y T L D H D R A I H I Q A E 6 24 L D H D R A I H I Q A E N G
P 6 29 A I H I Q A E N G P H L L V E 6 33 Q A E N G P H L L V E A E
Q A 6 34 A E N G P H L L V E A E Q A K 6 51 S H R G G N V T L P C K
F Y R 6 53 R G G N V T L P C K F Y R D P 6 58 T L P C K F Y R D P T
A F G S 6 62 K F Y R D P T A F G S G I H K 6 76 K I R I K W T K L T
S D Y L K 6 83 K L T S D Y L K E V D V F V S 6 90 K E V D V F V S M
G Y H K K T 6 96 V S M G Y H K K T Y G G Y Q G 6 99 G Y H K K T Y G
G Y Q G R V F 6 108 Y Q G R V F L K G G S D S D A 6 112 V F L K G G
S D S D A S L V I 6 122 A S L V I T D L T L E D Y G R 6 124 L V I T
D L T L E D Y G R Y K 6 125 V I T D L T L E D Y G R Y K C 6 133 D Y
G R Y K C E V I E G L E D 6 138 K C E V I E G L E D D T V V V 6 164
F P R L G R Y N L N F H E A Q 6 175 H E A Q Q A C L D Q D A V I A 6
176 E A Q Q A C L D Q D A V I A S 6 181 C L D Q D A V I A S F D Q L
Y 6 185 D A V I A S F D Q L Y D A W R 6 186 A V I A S F D Q L Y D A
W R G 6 197 A W R G G L D W C N A G W L S 6 199 R G G L D W C N A G
W L S D G 6 202 L D W C N A G W L S D G S V Q 6 203 D W C N A G W L
S D G S V Q Y 6 204 W C N A G W L S D G S V Q Y P 6 212 D G S V Q Y
P I T K P R E P C 6 217 Y P I T K P R E P C G G Q N T 6 223 R E P C
G G Q N T V P G V R N 6 232 V P G V R N Y G F W D K D K S 6 256 N F
N G R F Y Y L I H P T K L 6 262 Y Y L I H P T K L T Y D E A V 6 272
Y D E A V Q A C L N D G A Q I 6 274 E A V Q A C L N D G A Q I A K 6
277 Q A C L N D G A Q I A K V G Q 6 292 I F A A W K I L G Y D R C D
A 6 301 Y D R C D A G W L A D G S V R 6 302 D R C D A G W L A D G S
V R Y 6 303 R C D A G W L A D G S V R Y P 6 319 S R P R R R C S P T
E A A V R 6 320 R P R R R C S P T E A A V R F 6 326 S P T E A A V R
F V G F P D K 6 338 P D K K H K L Y G V Y C F R A 6 227 G G Q N T V
P G V R N Y G F W 4 64 Y R D P T A F G S G I H K I R 3 87 D Y L K E
V D V F V S M G Y H 3 225 P C G G Q N T V P G V R N Y G 3 282 D G A
Q I A K V G Q I F A A W 3 324 R C S P T E A A V R F V G F P 3 330 A
A V R F V G F P D K K H K L 3 42 V E A E Q A K V F S H R G G N 2 50
F S H R G G N V T L P C K F Y 2 52 H R G G N V T L P C K F Y R D 2
55 G N V T L P C K F Y R D P T A 2 66 D P T A F G S G I H K I R I K
2 69 A F G S G I H K I R I K W T K 2 100 Y H K K T Y G G Y Q G R V
F L 2 101 H K K T Y G G Y Q G R V F L K 2 143 E G L E D D T V V V A
L D L Q 2 152 V A L D L Q G V V F P Y F P R 2 159 V V F P Y F P R L
G R Y N L N 2 180 A C L D Q D A V I A S F D Q L 2 208 G W L S D G S
V Q Y P I T K P 2 243 K D K S R Y D V F C F T S N F 2 323 R R C S P
T E A A V R F V G F 2 328 T E A A V R F V G F P D K K H 2 340 K K H
K L Y G V Y C F R A Y N 2 14 W A D H L S D N Y T L D H D R 1 22 Y T
L D H D R A I H I Q A E N 1 30 I H I Q A E N G P H L L V E A 1 32 I
Q A E N G P H L L V E A E Q 1 59 L P C K F Y R D P T A F G S G 1 79
I K W T K L T S D Y L K E V D 1 80 K W T K L T S D Y L K E V D V 1
84 L T S D Y L K E V D V F V S M 1 104 T Y G G Y Q G R V F L K G G
S 1 114 L K G G S D S D A S L V I T D 1 115 K G G S D S D A S L V I
T D L 1 116 G G S D S D A S L V I T D L T 1 127 T D L T L E D Y G R
Y K C E V 1 132 E D Y G R Y K C E V I E G L E 1 140 E V I E G L E D
D T V V V A L 1 141 V I E G L E D D T V V V A L D 1 155 D L Q G V V
F P Y F P R L G R 1 162 P Y F P R L G R Y N L N F H E 1 170 Y N L N
F H E A Q Q A C L D Q 1 172 L N F H E A Q Q A C L D Q D A 1 177 A Q
Q A C L D Q D A V I A S F 1 187 V I A S F D Q L Y D A W R G G 1 205
C N A G W L S D G S V Q Y P I 1 210 L S D G S V Q Y P I T K P R E 1
230 N T V P G V R N Y G F W D K D 1 233 P G V R N Y G F W D K D K S
R 1 236 R N Y G F W D K D K S R Y D V 1 240 F W D K D K S R Y D V F
C F T 1 249 D V F C F T S N F N G R F Y Y 1 251 F C F T S N F N G R
F Y Y L I 1 253 F T S N F N G R F Y Y L I H P 1 255 S N F N G R F Y
Y L I H P T K 1 257 F N G R F Y Y L I H P T K L T 1 266 H P T K L T
Y D E A V Q A C L 1 271 T Y D E A V Q A C L N D G A Q 1 278 A C L N
D G A Q I A K V G Q I 1 287 A K V G Q I F A A W K I L G Y 1 288 K V
G Q I F A A W K I L G Y D 1 294 A A W K I L G Y D R C D A G W 1 304
C D A G W L A D G S V R Y P I 1 309 L A D G S V R Y P I S R P R R 1
322 R R R C S P T E A A V R F V G 1 337 F P D K K H K L Y G V Y C F
R 1 151P3D4 v.2: HLA Peptide Scoring Results DRB1*1101 15-mers
SYFPEITHI 229 P R G L G F I F K T I A P L A 27 137 S R I F W R Q E
K A D G G S C 24 44 T G I I T Q G A K D F G H V Q 22 51 A K D F G H
V Q F V G S Y K L 22 158 S E A Y K K V C L S G A P H E 22 233 G F I
F K T I A P L A A T R A 22 244 A T R A T R I G H P G G R T P 22 301
S S T Y D S L S P Y G P R N P 22 338 G Q K H N V L A R G K P Q R K
22 34 K V D L L V P T K V T G I I T 21 112 L K Y L A F L H K R M N
T N P 21 163 K V C L S G A P H E V G W K Y 21 181 T A T L E E K R K
E K A E I H 21 14 L H I V V E S I R D H S G Q K 20 40 P T K V T G I
I T Q G A K D F 20 111 K L K Y L A F L H K R M N T N 20 199 N K Q L
M R L Q K Q A E K N M 20 236 F K T I A P L A A T R A T R I 20 313 R
N P L P N P R H S P S G G G 20 130 P Y H F Q V P S R I F W R Q E 19
380 W K A I E S L E E G L G G K Q 19 15 H I V V E S I R D H S G Q K
M 18 56 H V Q F V G S Y K L A Y S N D 18 217 I D K Y T E S P G G G
S P R G 18 357 N N S W Y V E N G R P A D L A 18 358 N S W Y V E N G
R P A D L A G 18 174 G W K Y Q A V T A T L E E K R 17 60 V G S Y K
L A Y S N D G E H W 16 73 H W T V Y Q D E K Q R K D K V 16 138 R I
F W R Q E K A D G G S C C 16 281 P A A W L P L R T P W T R P S 16
285 L P L R T P W T R P S S C P T 16 377 G A L W K A I E S L E E G
L G 16 11 L R A L H I V V E S I R D H S 15 32 D K K V D L L V P T K
V T G I 15 82 Q R K D K V L L G R K A V V V 15 84 K D K V L L G R K
A V V V S C 15 89 L G R K A V V V S C E G I N I 15 105 G S F C R N
K L K Y L A F L H 15 119 H K R M N T N P S R R P Y H F 15 168 G A P
H E V G W K Y Q A V T A 15 207 K Q A E K N M K K K I D K Y T 15 222
E S P G G G S P R G L G F I F 15 257 T P R A G S S A H R P P A L S
15 344 L A R G K P Q R K P K S E N N 15 373 S G Y C G A L W K A I E
S L E 15 387 E E G L G G K Q K D K E R K A 15 26 G Q K M K Q D K K
V D L L V P 14 71 G E H W T V Y Q D E K Q R K D 14 83 R K D K V L L
G R K A V V V S 14 128 R R P Y H F Q V P S R I F W R 14 196 Y R K N
K Q L M R L Q K Q A E 14 211 K N M K K K I D K Y T E S P G 14 232 L
G F I F K T I A P L A A T R 14 251 G H P G G R T P R A G S S A H 14
258 P R A G S S A H R P P A L S A 14 312 P R N P L P N P R H S P S
G G 14 322 S P S G G G G L K K P A R H C 14 323 P S G G G G L K K P
A R H C Q 14 326 G G G L K K P A R H C Q G Q K 14 327 G G L K K P A
R H C Q G Q K H 14 340 K H N V L A R G K P Q R K P K 14 356 E N N S
W Y V E N G R P A D L 14 8 T F P L R A L H I V V E S I R 13 29 M K
Q D K K V D L L V P T K V 13 54 F G H V Q F V G S Y K L A Y S 13 86
K V L L G R K A V V V S C E G 13 93 A V V V S C E G I N I S G S F
13 247 A T R I G H P G G R T P R A G 13 264 A H R P P A L S A R A P
V P A 13 279 A S P A A W L P L R T P W T R 13 284 W L P L R T P W T
R P S S C P 13 304 Y D S L S P Y G P R N P L P N 13 57 V Q F V G S
Y K L A Y S N D G 12 74 W T V Y Q D E K Q R K D K V L 12 95 V V S C
E G I N I S G S F C R 12 109 R N K L K Y L A F L H K R M N 12 115 L
A F L H K R M N T N P S R R 12 116 A F L H K R M N T N P S R R P 12
179 A V T A T L E E K R K E K A E 12 214 K K K I D K Y T E S P G G
G S 12 267 P P A L S A R A P V P A A S P 12 270 L S A R A P V P A A
S P A A W 12 288 R T P W T R P S S C P T S S S 12 367 P A D L A G S
G Y C G A L W K 12 4 H T T K T F P L R A L H I V V 11 6 T K T F P L
R A L H I V V E S 11 120 K R M N T N P S R R P Y H F Q 11 2 L E H T
T K T F P L R A L H I 10 50 G A K D F G H V Q F V G S Y K 10 64 K L
A Y S N D G E H W T V Y Q 10 103 I S G S F C R N K L K Y L A F 10
104 S G S F C R N K L K Y L A F L 10 114 Y L A F L H K R M N T N P
S R 10 172 E V G W K Y Q A V T A T L E E 10 187 K R K E K A E I H Y
R K N K Q 10 193 E I H Y R K N K Q L M R L Q K 10 231 G L G F I F K
T I A P L A A T 10 241 P L A A T R A T R I G H P G G 10 307 L S P Y
G P R N P L P N P R H 10 336 C Q G Q K H N V L A R G K P Q 10 372 G
S G Y C G A L W K A I E S L 10 389 G L G G K Q K D K E R K A E N 10
7 K T F P L R A L H I V V E S I 9 12 R A L H I V V E S I R D H S G
9 20 S I R D H S G Q K M K Q D K K 9 25 S G Q K M K Q D K K V D L L
V 9 36 D L L V P T K V T G I I T Q G 9 37 L L V P T K V T G I I T Q
G A 9 55 G H V Q F V G S Y K L A Y S N 9 76 V Y Q D E K Q R K D K V
L L G 9 78 Q D E K Q R K D K V L L G R K 9 101 I N I S G S F C R N
K L K Y L 9 113 K Y L A F L H K R M N T N P S 9 129 R P Y H F Q V P
S R I F W R Q 9 154 Q G H A S E A Y K K V C L S G 9 177 Y Q A V T A
T L E E K R K E K 9 190 E K A E I H Y R K N K Q L M R 9 192 A E I H
Y R K N K Q L M R L Q 9 206 Q K Q A E K N M K K K I D K Y 9 333 A R
H C Q G Q K H N V L A R G 9 385 S L E E G L G G K Q K D K E R 9 398
E R K A E N G P H L L V E A E 9 10 P L R A L H I V V E S I R D H 8
13 A L H I V V E S I R D H S G Q 8 16 I V V E S I R D H S G Q K M K
8 22 R D H S G Q K M K Q D K K V D 8 48 T Q G A K D F G H V Q F V G
S 8 65 L A Y S N D G E H W T V Y Q D 8 75 T V Y Q D E K Q R K D K V
L
L 8 81 K Q R K D K V L L G R K A V V 8 88 L L G R K A V V V S C E G
I N 8 91 R K A V V V S C E G I N I S G 8 121 R M N T N P S R R P Y
H F Q V 8 124 T N P S R R P Y H F Q V P S R 8 132 H F Q V P S R I F
W R Q E K A 8 134 Q V P S R I F W R Q E K A D G 8 148 G G S C C P Q
G H A S E A Y K 8 155 G H A S E A Y K K V C L S G A 8 157 A S E A Y
K K V C L S G A P H 8 178 Q A V T A T L E E K R K E K A 8 180 V T A
T L E E K R K E K A E I 8 183 T L E E K R K E K A E I H Y R 8 188 R
K E K A E I H Y R K N K Q L 8 189 K E K A E I H Y R K N K Q L M 8
203 M R L Q K Q A E K N M K K K I 8 208 Q A E K N M K K K I D K Y T
E 8 220 Y T E S P G G G S P R G L G F 8 238 T I A P L A A T R A T R
I G H 8 239 I A P L A A T R A T R I G H P 8 240 A P L A A T R A T R
I G H P G 8 248 T R I G H P G G R T P R A G S 8 249 R I G H P G G R
T P R A G S S 8 253 P G G R T P R A G S S A H R P 8 256 R T P R A G
S S A H R P P A L 8 263 S A H R P P A L S A R A P V P 8 265 H R P P
A L S A R A P V P A A 8 269 A L S A R A P V P A A S P A A 8 280 S P
A A W L P L R T P W T R P 8 283 A W L P L R T P W T R P S S C 8 295
S S C P T S S S T Y D S L S P 8 305 D S L S P Y G P R N P L P N P 8
310 Y G P R N P L P N P R H S P S 8 332 P A R H C Q G Q K H N V L A
R 8 341 H N V L A R G K P Q R K P K S 8 342 N V L A R G K P Q R K P
K S E 8 343 V L A R G K P Q R K P K S E N 8 346 R G K P Q R K P K S
E N N S W 8 390 L G G K Q K D K E R K A E N G 8 391 G G K Q K D K E
R K A E N G P 8 392 G K Q K D K E R K A E N G P H 8 5 T T K T F P L
R A L H I V V E 7 18 V E S I R D H S G Q K M K Q D 7 23 D H S G Q K
M K Q D K K V D L 7 33 K K V D L L V P T K V T G I I 7 79 D E K Q R
K D K V L L G R K A 7 85 D K V L L G R K A V V V S C E 7 90 G R K A
V V V S C E G I N I S 7 100 G I N I S G S F C R N K L K Y 7 125 N P
S R R P Y H F Q V P S R I 7 133 F Q V P S R I F W R Q E K A D 7 135
V P S R I F W R Q E K A D G G 7 136 P S R I F W R Q E K A D G G S 7
156 H A S E A Y K K V C L S G A P 7 159 E A Y K K V C L S G A P H E
V 7 170 P H E V G W K Y Q A V T A T L 7 197 R K N K Q L M R L Q K Q
A E K 7 230 R G L G F I F K T I A P L A A 7 250 I G H P G G R T P R
A G S S A 7 260 A G S S A H R P P A L S A R A 7 266 R P P A L S A R
A P V P A A S 7 271 S A R A P V P A A S P A A W L 7 275 P V P A A S
P A A W L P L R T 7 297 C P T S S S T Y D S L S P Y G 7 306 S L S P
Y G P R N P L P N P R 7 311 G P R N P L P N P R H S P S G 7 321 H S
P S G G G G L K K P A R H 7 334 R H C Q G Q K H N V L A R G K 7 337
Q G Q K H N V L A R G K P Q R 7 360 W Y V E N G R P A D L A G S G 7
371 A G S G Y C G A L W K A I E S 7 376 C G A L W K A I E S L E E G
L 7 383 I E S L E E G L G G K Q K D K 7 9 F P L R A L H I V V E S I
R D 6 31 Q D K K V D L L V P T K V T G 6 35 V D L L V P T K V T G I
I T Q 6 39 V P T K V T G I I T Q G A K D 6 41 T K V T G I I T Q G A
K D F G 6 43 V T G I I T Q G A K D F G H V 6 59 F V G S Y K L A Y S
N D G E H 6 62 S Y K L A Y S N D G E H W T V 6 70 D G E H W T V Y Q
D E K Q R K 6 92 K A V V V S C E G I N I S G S 6 94 V V V S C E G I
N I S G S F C 6 97 S C E G I N I S G S F C R N K 6 98 C E G I N I S
G S F C R N K L 6 106 S F C R N K L K Y L A F L H K 6 126 P S R R P
Y H F Q V P S R I F 6 139 I F W R Q E K A D G G S C C P 6 142 R Q E
K A D G G S C C P Q G H 6 144 E K A D G G S C C P Q G H A S 6 146 A
D G G S C C P Q G H A S E A 6 147 D G G S C C P Q G H A S E A Y 6
149 G S C C P Q G H A S E A Y K K 6 160 A Y K K V C L S G A P H E V
G 6 161 Y K K V C L S G A P H E V G W 6 167 S G A P H E V G W K Y Q
A V T 6 171 H E V G W K Y Q A V T A T L E 6 191 K A E I H Y R K N K
Q L M R L 6 198 K N K Q L M R L Q K Q A E K N 6 200 K Q L M R L Q K
Q A E K N M K 6 202 L M R L Q K Q A E K N M K K K 6 210 E K N M K K
K I D K Y T E S P 6 212 N M K K K I D K Y T E S P G G 6 213 M K K K
I D K Y T E S P G G G 6 215 K K I D K Y T E S P G G G S P 6 216 K I
D K Y T E S P G G G S P R 6 218 D K Y T E S P G G G S P R G L 6 226
G G S P R G L G F I F K T I A 6 242 L A A T R A T R I G H P G G R 6
243 A A T R A T R I G H P G G R T 6 252 H P G G R T P R A G S S A H
R 6 261 G S S A H R P P A L S A R A P 6 268 P A L S A R A P V P A A
S P A 6 272 A R A P V P A A S P A A W L P 6 273 R A P V P A A S P A
A W L P L 6 282 A A W L P L R T P W T R P S S 6 287 L R T P W T R P
S S C P T S S 6 289 T P W T R P S S C P T S S S T 6 290 P W T R P S
S C P T S S S T Y 6 291 W T R P S S C P T S S S T Y D 6 298 P T S S
S T Y D S L S P Y G P 6 300 S S S T Y D S L S P Y G P R N 6 308 S P
Y G P R N P L P N P R H S 6 314 N P L P N P R H S P S G G G G 6 315
P L P N P R H S P S G G G G L 6 316 L P N P R H S P S G G G G L K 6
317 P N P R H S P S G G G G L K K 6 348 K P Q R K P K S E N N S W Y
V 6 354 K S E N N S W Y V E N G R P A 6 359 S W Y V E N G R P A D L
A G S 6 361 Y V E N G R P A D L A G S G Y 6 362 V E N G R P A D L A
G S G Y C 6 363 E N G R P A D L A G S G Y C G 6 364 N G R P A D L A
G S G Y C G A 6 366 R P A D L A G S G Y C G A L W 6 374 G Y C G A L
W K A I E S L E E 6 378 A L W K A I E S L E E G L G G 6 381 K A I E
S L E E G L G G K Q K 6 384 E S L E E G L G G K Q K D K E 6 393 K Q
K D K E R K A E N G P H L 6 394 Q K D K E R K A E N G P H L L 6 400
K A E N G P H L L V E A E Q A 6 1 M L E H T T K T F P L R A L H 3
28 K M K Q D K K V D L L V P T K 3 166 L S G A P H E V G W K Y Q A
V 3 53 D F G H V Q F V G S Y K L A Y 2 69 N D G E H W T V Y Q D E K
Q R 2 80 E K Q R K D K V L L G R K A V 2 87 V L L G R K A V V V S C
E G I 2 99 E G I N I S G S F C R N K L K 2 118 L H K R M N T N P S
R R P Y H 2 173 V G W K Y Q A V T A T L E E K 2 194 I H Y R K N K Q
L M R L Q K Q 2 195 H Y R K N K Q L M R L Q K Q A 2 234 F I F K T I
A P L A A T R A T 2 246 R A T R I G H P G G R T P R A 2 278 A A S P
A A W L P L R T P W T 2 299 T S S S T Y D S L S P Y G P R 2 303 T Y
D S L S P Y G P R N P L P 2 324 S G G G G L K K P A R H C Q G 2 355
S E N N S W Y V E N G R P A D 2 3 E H T T K T F P L R A L H I V 1
24 H S G Q K M K Q D K K V D L L 1 27 Q K M K Q D K K V D L L V P T
1 30 K Q D K K V D L L V P T K V T 1 38 L V P T K V T G I I T Q G A
K 1 42 K V T G I I T Q G A K D F G H 1 47 I T Q G A K D F G H V Q F
V G 1 52 K D F G H V Q F V G S Y K L A 1 66 A Y S N D G E H W T V Y
Q D E 1 77 Y Q D E K Q R K D K V L L G R 1 102 N I S G S F C R N K
L K Y L A 1 108 C R N K L K Y L A F L H K R M 1 110 N K L K Y L A F
L H K R M N T 1 152 C P Q G H A S E A Y K K V C L 1 153 P Q G H A S
E A Y K K V C L S 1 175 W K Y Q A V T A T L E E K R K 1 184 L E E K
R K E K A E I H Y R K 1 201 Q L M R L Q K Q A E K N M K K 1 204 R L
Q K Q A E K N M K K K I D 1 205 L Q K Q A E K N N K K K I D K 1 209
A E K N M K K K I D K Y T E S 1 221 T E S P G G G S P R G L G F I 1
225 G G G S P R G L G F I F K T I 1 227 G S P R G L G F I F K T I A
P 1 237 K T I A P L A A T R A T R I G 1 277 P A A S P A A W L P L R
T P W 1 319 P R H S P S G G G G L K K P A 1 320 R H S P S G G G G L
K K P A R 1 325 G G G G L K K P A R H C Q G Q 1 330 K K P A R H C Q
G Q K H N V L 1 352 K P K S E N N S W Y V E N G R 1 369 D L A G S G
Y C G A L W K A I 1 397 K E R K A E N G P H L L V E A 1 399 R K A K
N G P H L L V E A E Q 1
[0852]
59 TABLE LII Exon Number Start End (A). Exon compositions of
151P3D4 v.1 Exon 1 1 289 Exon 2 290 415 Exon 3 416 787 Exon 4 788
1090 Exon 5 1091 1957 (B). Exon compositions of 151P3D4 v.2 Exon 1
1 102 Exon 2 103 258 Exon 3 259 425 Exon 4 426 667 Exon 5 668 863
Exon 6 864 999 Exon 7 1000 1201 Exon 8 1202 1573 Exon 9 1574 1876
Exon 10 1877 2166
[0853]
60TABLE LIII Nucleotide sequence of transcript variant 151P3D4 v.2
atgttggagc atactactaa gacattcccc ttaagagcac tgcacatagt tgtggaaagc
60 attagggacc acagtggcca aaaaatgaag caggataaga aggtggatct
tcttgttcca 120 accaaagtga ctggcatcat tacacaagga gctaaagatt
ttggtcatgt acagtttgtt 180 ggctcctaca aactggctta cagcaatgat
ggagaacact ggactgtata ccaggatgaa 240 aagcaaagaa aagataaggt
actgctgggc cggaaggcgg tggtcgtaag ctgcgaaggc 300 atcaacattt
ctggcagttt ctgcagaaac aagttgaagt acctggcttt cctccacaag 360
cggatgaaca ccaacccttc tcgacgcccc taccacttcc aggtccccag ccgcatcttc
420 tggcgacaag aaaaagcaga tggtggttcc tgctgccctc aaggtcatgc
gtctgaagcc 480 tacaagaaag tttgcctatc tggggcgcct cacgaggttg
gctggaagta ccaggcagtg 540 acagccaccc tggaggaaaa gaggaaagag
aaagccgaga tccactaccg gaagaataaa 600 cagctcatga ggctacagaa
acaggccgag aagaacatga agaagaaaat tgacaaatac 660 acagagagtc
caggaggagg cagtccccgt ggcttaggct ttatctttaa gacaatagcg 720
ccgctcgccg ccacccgcgc gactcggatc gggcatcccg gcggccgcac cccgcgcgct
780 ggctcatctg cacaccggcc acctgcattg tcggccagag cccccgtccc
ggcggcttcc 840 ccagcagctt ggctgcccct caggacgccc tggacccgcc
catcctcctg ccccactagc 900 tcatcgactt acgactccct cagtccctac
ggcccacgga accctctccc caacccgcgc 960 cacagcccga gcggcggcgg
cggccttaag aagcccgcaa gacactgtca aggtcaaaag 1020 cacaatgtgc
tagccagggg gaaaccccag agaaagccaa aatctgaaaa taacagctgg 1080
tatgtagaaa acggcagacc tgctgacttg gcaggctcag gatattgtgg tgctctttgg
1140 aaggcaatag agtccttgga ggaaggactt ggaggaaaac aaaaggacaa
ggaaaggaaa 1200 gcagaaaatg gcccccatct acttgtggaa gcagagcaag
ccaaggtgtt ttcacacaga 1260 ggtggcaatg ttacactgcc atgtaaattt
tatcgagacc ctacagcatt tggctcagga 1320 atccataaaa tccgaattaa
gtggaccaag ctaacttcgg attacctcaa ggaagtggat 1380 gtttttgttt
ccatgggata ccacaaaaaa acctatggag gctaccaggg tagagtgttt 1440
ctgaagggag gcagtgatag tgatgcttct ctggtcatca cagacctcac tctggaagat
1500 tatgggagat ataagtgtga ggtgattgaa ggattagaag atgatactgt
tgtggtagca 1560 ctggacttac aaggtgtggt attcccttac tttccacgac
tggggcgcta caatctcaat 1620 tttcacgagg cgcagcaggc gtgtctggac
caggatgctg tgatcgcctc cttcgaccag 1680 ctgtacgacg cctggcgggg
cgggctggac tggtgcaatg ccggctggct cagtgatggc 1740 tctgtgcaat
atcccatcac aaagcccaga gagccctgtg gggggcagaa cacagtgccc 1800
ggagtcagga actacggatt ttgggataaa gataaaagca gatatgatgt tttctgtttt
1860 acatccaatt tcaatggccg tttttactat ctgatccacc ccaccaaact
gacctatgat 1920 gaagcggtgc aagcttgtct caatgatggt gctcagattg
caaaagtggg ccagatattt 1980 gctgcctgga aaattctcgg atatgaccgc
tgtgatgcgg gctggttggc ggatggcagc 2040 gtccgctacc ccatctctag
gccaagaagg cgctgcagtc ctactgaggc tgcagtgcgc 2100 ttcgtgggtt
tcccagataa aaagcataag ctgtatggtg tctactgctt cagagcatac 2160 aactga
2166
[0854]
61TABLE LIV Nucleotide sequence alignment of 1Z1P1F1 v.1 and
151P3D4 v.2 151P3D4v.1
------------------------------------------------------------
151P3D4v.2
ATGTTGGAGCATACTACTAAGACATTCCCCTTAAGAGCACTGCACATAGTTGTGGAAA- GC 60
151P3D4v.1 ------------------------------------------
------------------- 151P3D4v.2 ATTAGGGACCACAGTGGCCAAAAAATG-
AAGCAGGATAAGAAGGTGGATCTTCTTGTTCCA 120 151P3D4v.1
------------------------------------------------------------
151P3D4v.2
ACCAAAGTGACTGGCATCATTACACAAGGAGCTAAAGATTTTGGTCATGTACAGTTTGT- T 180
151P3D4v.1 ------------------------------------------
------------------- 151P3D4v.2 GGCTCCTACAAACTGGCTTACAGCAAT-
GATGGAGAACACTGGACTGTATACCAGGATGAA 240 151P3D4v.1
------------------------------------------------------------
151P3D4v.2
AAGCAAAGAAAAGATAAGGTACTGCTGGGCCGGAAGGCGCTGGTCGTAAGCTGCGAAGG- C 300
151P3D4v.1 ------------------------------------------
------------------- 151P3D4v.2 ATCAACATTTCTGGCAGTTTCTGCAGA-
AACAAGTTGAAGTACCTGGCTTTCCTCCACAAG 360 151P3D4v.1
------------------------------------------------------------
151P3D4v.2
CGGATGAACACCAACCCTTCTCGACCCCCCTACCACTTCCAGCTCCCCAGCCGCATCTT- C 420
151P3D4V.1 ------------------------------------------
------------------- 151P3D4v.2 TGGCGACAAGAAAAAGCACATGGTGGT-
TCCTGCTCCCCTCAAGGTCATGCGTCTGAAGCC 480 151P3D4v.1
------------------------------------------------------------
151P3D4v.2
TACAAGAAAGTTTGCCTATCTGGGGCGCCTCACGAGGTTGGCTGGAAGTACCAGGCAGT- G 540
151P3D4v.1 ------------------------------------------
------------------- 151P3D4v.2 ACAGCCACCCTGCAGGAAAAGAGGAAA-
GAGAAAGCCGAGATCCACTACCGGAAGAATAAA 600 151P3D4v.1
------------------------------------------------------------
151P3D4v.2
ACAGCCACCCTGGAGGAAAAGAGGAAAGAGAAAGCCGAGATCCACTACCGGAAGAATAA- A 660
151P3D4v.1 ------------------------------------------
------------------- 151P3D4v.2 ACAGAGAGTCCAGGAGGAGGCAGTCCC-
CGTCGCTTAGGCTTTATCTTTAAGACAATAGCG 720 151P3D4v.1
----------------------------------------------TTAGGCTGTA-ATT 13
151P3D4v.2 CCGCTCGCCGCCACCCOCGCGACTCGGATCGGGCATCCCCGCGGCCGCACCCCGC-
GCGCT 780 * * * * 151P3D4v.1
AGGGGATTTGGGAGGAGA--ACTTTCCTGGTGACGCTTTGCT- TTTCTTCTGCT--CTTGG 69
151P3D4v.2 GGCTCATCTGCACACCGGCCACCTG-
CATTATCGGCCAGAGCCCCCGTCCCGGCGGCTTCC 840 * ** ** * ** * * * ** * **
* * * *** 151P3D4v.1
TCAGAAAGT-GCCTCCTTCTTCCCAGGATCAGGACCT--CTGCCATCCAGCGCCACAA-- 124
151P3D4v.2 CCAGCAGCTTGGCTGCCCCTCAGGACGCCCTGGACCCGCCCATCCTCCTGCCCCA-
CTAGC 900 ** * * * ** * ** * * * ***** * * *** ** **** * 151P3D4v.1
--AGAGACATTCTGCACACACACTCACACACACACACACACACA- CACTCTCACACTCCC- 181
151P3D4V.2 TCATCGACTTACGACTCCCTCAGTCC-
CTACGGCCCACGGA-ACCCTCTCCCCAACCCGCG 959 * *** * * * * * ** ** * *
*** * ** * *** * ** *** 151P3D4v.1
CCAGAGACAAACTTAACGTGAGG-----AGAAAGAGCGCTA--CGTTCACTTCATCTCCA 234
151P3D4V.2 CCACAGCCCGAGCGGCGGCGGCGGCCTTAAGAAGCCCGCAAGACACTGTCAAGGT-
CAAAA 1019 *** ** * * ** * * * *** *** * * * * * ** * 151P3D4v.1
GC------TTCCAACTTAAGCAGAACTTGAGAGCATCCG- AACTCCTGGATTTCAGGACAA 288
151P3D4v.2
GCACAATGTGCTAGCCAGGGGGAAACCCCAGAGAAAGCCAAAATCTGAAAATAACAGCTG 1079
** * * * * * *** **** * * ** *** * * * * 151P3D4v.1
GTGAAGAAGATTCTTTGGGC-TATAAAGATGA-AGAGTCTACTTCTTCTGGTGCTGATTT 346
151P3D4v.2 GTATGTAGAAAACGGCAGACCTCCTCACTTGGCAGGCTCAGG-
ATATTGTGGTGCTCTTTG 1139 ** * * * * * * * ** ** ** * ** ******* **
151P3D4v.1 CAATCTGCTGGGCTGATCATCTTTCAGAC-
AACTATACTCTGGATCATGACAGAGCTATTC 406 151P3D4v.2
GAAGGCAATACA------GTCCTTGGAGGAAGGACTTGGAGGAAAACAAAAGGACAAGGA 1193
** * * ** ** ** * *** * * ** * * 151P3D4v.1
ACATCCAAGCAGAAAATGGCCCCCATCTACTTGTGGAAGCAGAGCAAGCCAAGGTGTTTT 466
151P3D4v.2 A-AGGAAAGCAGAAAATGGCCCCCATCTACTTGTGGAAGCAG-
AOCAAGCCAAGGTGTTTT 1252 * * ************************************-
****************** 151P3D4v.1 CACACAGAGGTGGCAATGTTACACTGCC-
ATGTAAATTTTATCGAGACCCTACAGCATTTG 526 151P3D4v.2
CACACAGAGGTGGCAATGTTACACTCCCATGTAAATTTTATCGAGACCCTACAGCATTTG 1312
************************************************************
151P3D4v.1
GCTCAGGAATCCATAAAATCCGAATTAAGTGGACCAAGCTAACTTCGGATTACCTCAAG- G 586
151P3D4v.2 GCTCAGGAATCCATAAAATCCGAATTAAGTGGACCAAGCTA-
ACTTCGGATTACCTCAAGG 1372 *****************************************-
******************* 151P3D4v.1 AAGTGGATGTTTTTGTTTCCATGGGAT-
ACCACAAAAAAACCTATGGAGGCTACCAGGGTA 646 151P3D4v.2
AAGTGGATGTTTTTGTTTCCATGGGATACCACAAAAAAACCTATGGAGGCTACCAGGGTA 1432
************************************************************
151P3D4v.1
GAGTGTTTCTGAAGGGAGGCAGTGATAGTGATGCTTCTCTGGTCATCACAGACCTCACT- C 706
151P3D4v.2 GAGTGTTTCTGAAGGGAGGCAGTGATAGTGATGCTTCTCTG-
GTCATCACAGACCTCACTC 1492 *****************************************-
******************* 151P3D4v.1 TGGAAGATTAGGGGAGATATAAGTGTG-
AGGTGATTGAAGGATTAGAAGATGATACTGTTG 766 151P3D4v.2
TGGAAGATTATGGGAGATATAAGTGTGAGCTGATTGAAGGATTAGAAGATCATACTGTTG 1552
************************************************************
151P3D4v.1
TGGTAGCACTGCACTTACAAGGTGTCGTATTCCCTTACTTTCCACGACTCGGGCGCTAC- A 826
151P3D4v.2 TGGTAGCACTGGACTTACAAGGTCTGGTATTCCCTTACTTT-
CCACGACTGGGGCGCTACA 1612 *****************************************-
******************* 151P3D4v.1 ATCTCAATTTTCACGAGCCGCAGCAGG-
CGTGTCTGGACCAGGATGCTGTGATCGCCTCCT 886 151P3D4v.2
ATCTCAATTTTCACGAGGCGCAGCAGGCGTGTCTGGACCAGGATGCTGTGATCGCCTCCT 1672
************************************************************
151P3D4v.1
TCGACCAGCTGTACGACGCCTGGCGGGGCGGGCTGGACTGGTGCAATGCCCGCTGGCTC- A 946
151P3D4v.2 TCGACCAGCTGTACGACGCCTGGCGGGGCGGGCTGGACTGG-
TGCAATGCCGGCTGGCTCA 1732 *****************************************-
******************* 151P3D4v.1 GTGATGGCTCTGTGCAATATCCCATCA-
CAAAGCCCAGAGAGCCCTGTGGGGGCCAGAACA 1006 151P3D4v.2
GTGATGGCTCTGTGCAATATCCCATCACAAAGCCCAGAGAGCCCTGTGGGGGGCAGAACA 1792
**************************************************** *******
151P3D4v.1
CAGTGCCCGGAGTCAGGAACTACGGATTTTGGGATAAAGATAAAAGCAGATATGATGTT- T 1066
151P3D4v.2 CAGTGCCCGGAGTCAGGAACTACCGATTTTGGGATAAAGA-
TAAAAGCAGATATGATGTTT 1852 ****************************************-
******************** 151P3D4v.1 TCTGTTTTACATCCAATTTCAATGGC-
CGTTTTTACTATCTGATCCACCCCACCAAACTGA 1126 151P3D4v.2
TCTGTTTTACATCCAATTTCAATGGCCGTTTTTACTATCTGATCCACCCCACCAAACTGA 1912
************************************************************
151P3D4v.1
CCTATGATGAAGCGGTGCAAGCTTGTCTCAATGATGGTGCTCAGATTGCAAAAGTGGGC- C 1186
151P3D4v.2 CCTATGATGAAGCGGTGCAACCTTGTCTCAATGATGGTGC-
TCAGATTGCAAAAGTGGGCC 1972 ****************************************-
******************** 151P3D4v.1 AGATATTTGCTCCCTGGAAAATTCTC-
GGATATCACCGCTGTGATGCGGGCTGGTTGGCGG 1246 151P3D4v.2
AGATATTTGCTGCCTGGAAAATTCTCGGATATGACCGCTGTGATGCGGGCTGGTTGGCGG 2032
************************************************************
151P3D4v.1
ATGGCAGCGTCCGCTACCCCATCTCTAGGCCAAGAAGGCGCTGCAGTCCTACTGAGGCT- G 1306
151P3D4v.2 ATGGCAGCGTCCGCTACCCCATCTCTAGGCCAAGAAGGCG-
CTGCAGTCCTACTGACGCTG 2092 ****************************************-
******************** 151P3D4v.1 CAGTGCGCTTCGTGGGTTTCCCAGAT-
AAAAAGCATAAGCTGTATGGTGTCTACTGCTTCA 1366 151P3D4v.2
CAGTGCGCTTCGTGGGTTTCCCAGATAAAAAGCATAAGCTGTATGGTGTCTACTGCTTCA 2152
************************************************************
151P3D4v.1
GAGCATACAACTGAATGTGCCCTTAGAGCGCATCAGTTTTAAAGTCATTAAGAACATGT- G 1426
151P3D4v.2 GAGCATACAACTGA---------------------------
-------------------- 2166 ************** 151P3D4v.1
AAAGGTGTTTTTTTTTTCCAATATGAACTCATGCAAGTTACCAAAACTGTGATAACCCTT 1486
151P3D4v.2 ------------------------------------------
------------------- 151P3D4v.1 TTTTACTTACTGTAAAGAGTCATTTTC-
ATAAGATCAATTCATTGATTTGTTTTTTGTAAA 1546 151P3D4v.2
------------------------------------------------------------
151P3D4v.1
GCTATCATTCAATATATATTATAAATTAATATAAATTTAAGGCAAGCTCTATGTAAGGA- G 1606
151P3D4v.2 -----------------------------------------
-------------------- 151P3D4v.1 ACTTAGAGCCAAACTGTTTAAGCTGT-
ATCATCCCAACAAAGTATCCTTTCATGAACGGGG 1666 151PSD4v.2
------------------------------------------------------------
151P3D4v.1
CATGCAATAGCTTAAGAATTGCTACGATTAAATTAAGGAAACTAAAGCTACTCAGAGCA- A 1726
151P3D4v.2 -----------------------------------------
-------------------- 151P2D4v.1 CAGGTTCCACAAGCACAAACTTTACA-
CATTTGTACAATTTTCAAATGCACTACAATAAAC 1786 151P3D4v.2
------------------------------------------------------------
151P3D4v.1
AAATTAGAGCAACACATTTGAAATACAGGCTTCTTTACATAAACTGAGAGGTTATACAA- A 1846
151P3D4v.2 -----------------------------------------
-------------------- 151P3D4v.1 ACTCAGTTTCACAAGGGAACAATCTA-
TACCTTTCTAAAAGTTAATATTTCAAGTCTCTAA 1906 151PSD4v.2
------------------------------------------------------------
151P3D4v.1 TAGGCAGAATATTTTACTCTTTAAAATCCTGCCTTTCTGACCAAAAAAAAA 1957
151P3D4v.2 --------------------------------------------------
--
[0855]
62TABLE LV Amino acid sequence alignment of 121PJF1v.1 and
151P3D4v.2 151P3D4v.1
------------------------------------------------------------
151P3D4v.2
MLEHTTKTFPLRALHIVVESIRDNSGQKNKQDKKVDLLVPTKVTGIITQGAKDFGHVQ- FV 60
151P3D4v.1 ------------------------------------------
------------------- 151P3D4v.2 GSYKLAYSNDGEHWTVYQDEKQRKDKV-
LLGRKAVVVSCEGINISGSFCRNKLKYLAFLHK 120 151P3D4v.1
-------MKSLLLLVLISICWAdHLSDN-------------------------------- 21
151P3D4v.2 RMNTNPSRRPYHFQVPSRIFWRQEKADGGSCCPQGHASEAYKKVCLSGAPHEVGW-
KYQAV 180 :. : * * * :. :*. 151P3D4v.1
---------------------------------------YT-------------------
15123D4v.2
TATLEEKRKEKAEIHYRKNKQLMRLQKQAEKNMKKKIDKYTESPGCGSPRGLGFIFKTI- A 240
151P3D4v.1 -LDHDRAIMI--------------------------------
------------------- 32 151P3D4v.2 PLAATRATRIGHPGGRTPRAGSSA-
HRPPALSARAPVPAASPAAWLPLRTPWTRPSSCPTS 300 * ** :* 151P3D4v.1
------------------------------------------------------------
151PSD4v.2 SSTYDSLSPYGPRNPLPNPRHSPSGGGGLKKPARHCQGQKHNVLAR-
GKPQRKPKSENNSW 360 151P3D4v.1 -----------------------------
-----------QAENGPHLLVEAEQAKVPSHR 53 151P3D4V.2
YVENGRPADLAGSGYCGALWKAIESLEEGLGGKQKDKERKAENGPHLLVEAEQAKVFSHR 420
******************** 151P3D4v.1
GGNVTLPCKFYRDPTAFGSGIHKIRIKWTKLTSDYLKEVDVFVSMGYHKKTYGGYQGRVF 113
151P3D4v.2 GGNVTLPCKFYRDPTAFGSGTHKIRIKWTKLTSDYLKEVDVF-
VSMGYNKKTYGGYQGRVF 480 *******************************************-
***************** 151P3D4v.1 LKGGSDSDASLVITDLTLEDYGRYKCEVI-
EGLEDDTVVVALDLQGVVFPYFPRLGRYNLN 173 151P3D4v.2
LKGGSDSDASLVITDLTLEDYGRYKCEVIEGLEDDTVVVALDLQGVVFPYFPRLGRYNLN 540
************************************************************
151P3D4v.1
FHEAQQACLDQDAVIASFDQLYDAWRGGLDWCNAGWLSDGSVQYPITKPREPCGGQNTV- P 233
151P3D4v.2 FHEAQQACLDQDAVIASFDQLYDAWRGGLDWCNAGWLSDGS-
VQYPITKPREPCGGQNTVP 600 ******************************************-
****************** 151P3D4v.1 GVRNYGFWDkDKSRYDVFCFTSNFNGRF-
YYLIHPTKLTYDEAVQACLNDGAQIAKVGQIF 293 151P3D4v.2
GVRNYGFWDKDKSRYDVFCFTSNFNGRFYYLIHPTKLTYDEAVQACLNDGAQIAKVGQIF 660
************************************************************
151P3D4v.1
AAWKILGYDRCDACWLADGSVRYPISRPRRRCSPTEAAVRFVGFPDKKHKLYGVYCFRA- Y 353
151P3D4v.2 AAWKILGYDRCDAGWLADGSVRYPISRPRRRCSPTEAAVRP-
VGFPDKKNKLYGVYCFRAY 720 ******************************************-
****************** 151P3D4v.1 N 354 151P3D4v.2 N 721
[0856]
Sequence CWU 1
1
67 1 417 DNA Homo sapiens misc_feature 393 n = a, t, c, or g 1
gatccacccc accaaactga cctatgatga agcggtgcaa gcttgtctca atgatggtgc
60 tcagattgca aaagtgggcc agatatttgc tgcctggaaa attctcggat
atgaccgctg 120 tgatgcgggc tggttggcgg atggcagcgt ccgctacccc
atctctaggc caagaaggcg 180 ctgcagtcct actgaggctg cagtgcgctt
cgtgggtttc ccagataaaa agcataagct 240 gtatggtgtc tactgcttca
gagcatacaa ctgaatgtgc ccttagagcg catcagtttt 300 aaagtcatta
agaacatgtg aaaggtgttt tttttttcca atatgaactc atgcaagtta 360
ccaaaactgt gataaccctt ttttacttac tgnaaagaag tcattttcat aaagatc 417
2 1957 DNA Homo sapiens CDS (316)...(1380) 2 ttaggctgta attaggggat
ttgggaggag aactttcctg gtgacgcttt gcttttcttc 60 tgctcttggt
gagaaagtgc ctccttcttc ccaggatcag gacctctgcc atccagcgcc 120
acaaagagac attctgcaca cacactcaca cacacacaca cacacacact ctcacactcg
180 cccagagaca aacttaaggt gaggagaaag agcgctacgt tcacttgatc
tccagcttcc 240 aacttaagca gaacttgaga gcatccgaac tcctggattt
caggacaagt gaagaagatt 300 ctttgggcta taaag atg aag agt cta ctt ctt
ctg gtg ctg att tca atc 351 Met Lys Ser Leu Leu Leu Leu Val Leu Ile
Ser Ile 1 5 10 tgc tgg gct gat cat ctt tca gac aac tat act ctg gat
cat gac aga 399 Cys Trp Ala Asp His Leu Ser Asp Asn Tyr Thr Leu Asp
His Asp Arg 15 20 25 gct att cac atc caa gca gaa aat ggc ccc cat
cta ctt gtg gaa gca 447 Ala Ile His Ile Gln Ala Glu Asn Gly Pro His
Leu Leu Val Glu Ala 30 35 40 gag caa gcc aag gtg ttt tca cac aga
ggt ggc aat gtt aca ctg cca 495 Glu Gln Ala Lys Val Phe Ser His Arg
Gly Gly Asn Val Thr Leu Pro 45 50 55 60 tgt aaa ttt tat cga gac cct
aca gca ttt ggc tca gga atc cat aaa 543 Cys Lys Phe Tyr Arg Asp Pro
Thr Ala Phe Gly Ser Gly Ile His Lys 65 70 75 atc cga att aag tgg
acc aag cta act tcg gat tac ctc aag gaa gtg 591 Ile Arg Ile Lys Trp
Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val 80 85 90 gat gtt ttt
gtt tcc atg gga tac cac aaa aaa acc tat gga ggc tac 639 Asp Val Phe
Val Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr 95 100 105 cag
ggt aga gtg ttt ctg aag gga ggc agt gat agt gat gct tct ctg 687 Gln
Gly Arg Val Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu 110 115
120 gtc atc aca gac ctc act ctg gaa gat tat ggg aga tat aag tgt gag
735 Val Ile Thr Asp Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu
125 130 135 140 gtg att gaa gga tta gaa gat gat act gtt gtg gta gca
ctg gac tta 783 Val Ile Glu Gly Leu Glu Asp Asp Thr Val Val Val Ala
Leu Asp Leu 145 150 155 caa ggt gtg gta ttc cct tac ttt cca cga ctg
ggg cgc tac aat ctc 831 Gln Gly Val Val Phe Pro Tyr Phe Pro Arg Leu
Gly Arg Tyr Asn Leu 160 165 170 aat ttt cac gag gcg cag cag gcg tgt
ctg gac cag gat gct gtg atc 879 Asn Phe His Glu Ala Gln Gln Ala Cys
Leu Asp Gln Asp Ala Val Ile 175 180 185 gcc tcc ttc gac cag ctg tac
gac gcc tgg cgg ggc ggg ctg gac tgg 927 Ala Ser Phe Asp Gln Leu Tyr
Asp Ala Trp Arg Gly Gly Leu Asp Trp 190 195 200 tgc aat gcc ggc tgg
ctc agt gat ggc tct gtg caa tat ccc atc aca 975 Cys Asn Ala Gly Trp
Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr 205 210 215 220 aag ccc
aga gag ccc tgt ggg ggc cag aac aca gtg ccc gga gtc agg 1023 Lys
Pro Arg Glu Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg 225 230
235 aac tac gga ttt tgg gat aaa gat aaa agc aga tat gat gtt ttc tgt
1071 Asn Tyr Gly Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe
Cys 240 245 250 ttt aca tcc aat ttc aat ggc cgt ttt tac tat ctg atc
cac ccc acc 1119 Phe Thr Ser Asn Phe Asn Gly Arg Phe Tyr Tyr Leu
Ile His Pro Thr 255 260 265 aaa ctg acc tat gat gaa gcg gtg caa gct
tgt ctc aat gat ggt gct 1167 Lys Leu Thr Tyr Asp Glu Ala Val Gln
Ala Cys Leu Asn Asp Gly Ala 270 275 280 cag att gca aaa gtg ggc cag
ata ttt gct gcc tgg aaa att ctc gga 1215 Gln Ile Ala Lys Val Gly
Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly 285 290 295 300 tat gac cgc
tgt gat gcg ggc tgg ttg gcg gat ggc agc gtc cgc tac 1263 Tyr Asp
Arg Cys Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr 305 310 315
ccc atc tct agg cca aga agg cgc tgc agt cct act gag gct gca gtg
1311 Pro Ile Ser Arg Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala
Val 320 325 330 cgc ttc gtg ggt ttc cca gat aaa aag cat aag ctg tat
ggt gtc tac 1359 Arg Phe Val Gly Phe Pro Asp Lys Lys His Lys Leu
Tyr Gly Val Tyr 335 340 345 tgc ttc aga gca tac aac tga atgtgccctt
agagcgcatc agttttaaag 1410 Cys Phe Arg Ala Tyr Asn * 350 tcattaagaa
catgtgaaag gtgttttttt tttccaatat gaactcatgc aagttaccaa 1470
aactgtgata accctttttt acttactgta aagagtcatt ttcataagat caattcattg
1530 atttgttttt tgtaaagcta tcattcaata tatattataa attaatataa
atttaaggga 1590 agctctatgt aaggagactt agagccaaac tgtttaagct
gtatcatccc aacaaagtat 1650 cctttcatga acggggcatg caatagctta
agaattgcta ggattaaatt aaggaaagta 1710 aagctactca gagcaacagg
ttccacaagc acaaacttta cacatttgta caattttgaa 1770 atgcactaca
ataaacaaat tagagcaaca catttgaaat acaggcttct ttacataaac 1830
tgagaggtta tacaaaactc agtttcacaa gggaacaatc tatacctttc taaaagttaa
1890 tatttcaagt ctctaatagg cagaatattt tactctttaa aatcctgcct
ttctgaccaa 1950 aaaaaaa 1957 3 354 PRT Homo sapiens 3 Met Lys Ser
Leu Leu Leu Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His
Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 20 25
30 Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys
35 40 45 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys
Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys
Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys
Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr
Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser
Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu
Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu
Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155
160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu
165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser
Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp
Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro
Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val
Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys
Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly
Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp
Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275 280
285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys
290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile
Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala
Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr
Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 4 2166 DNA Homo
sapiens CDS (1)...(2166) 4 atg ttg gag cat act act aag aca ttc ccc
tta aga gca ctg cac ata 48 Met Leu Glu His Thr Thr Lys Thr Phe Pro
Leu Arg Ala Leu His Ile 1 5 10 15 gtt gtg gaa agc att agg gac cac
agt ggc caa aaa atg aag cag gat 96 Val Val Glu Ser Ile Arg Asp His
Ser Gly Gln Lys Met Lys Gln Asp 20 25 30 aag aag gtg gat ctt ctt
gtt cca acc aaa gtg act ggc atc att aca 144 Lys Lys Val Asp Leu Leu
Val Pro Thr Lys Val Thr Gly Ile Ile Thr 35 40 45 caa gga gct aaa
gat ttt ggt cat gta cag ttt gtt ggc tcc tac aaa 192 Gln Gly Ala Lys
Asp Phe Gly His Val Gln Phe Val Gly Ser Tyr Lys 50 55 60 ctg gct
tac agc aat gat gga gaa cac tgg act gta tac cag gat gaa 240 Leu Ala
Tyr Ser Asn Asp Gly Glu His Trp Thr Val Tyr Gln Asp Glu 65 70 75 80
aag caa aga aaa gat aag gta ctg ctg ggc cgg aag gcg gtg gtc gta 288
Lys Gln Arg Lys Asp Lys Val Leu Leu Gly Arg Lys Ala Val Val Val 85
90 95 agc tgc gaa ggc atc aac att tct ggc agt ttc tgc aga aac aag
ttg 336 Ser Cys Glu Gly Ile Asn Ile Ser Gly Ser Phe Cys Arg Asn Lys
Leu 100 105 110 aag tac ctg gct ttc ctc cac aag cgg atg aac acc aac
cct tct cga 384 Lys Tyr Leu Ala Phe Leu His Lys Arg Met Asn Thr Asn
Pro Ser Arg 115 120 125 cgc ccc tac cac ttc cag gtc ccc agc cgc atc
ttc tgg cga caa gaa 432 Arg Pro Tyr His Phe Gln Val Pro Ser Arg Ile
Phe Trp Arg Gln Glu 130 135 140 aaa gca gat ggt ggt tcc tgc tgc cct
caa ggt cat gcg tct gaa gcc 480 Lys Ala Asp Gly Gly Ser Cys Cys Pro
Gln Gly His Ala Ser Glu Ala 145 150 155 160 tac aag aaa gtt tgc cta
tct ggg gcg cct cac gag gtt ggc tgg aag 528 Tyr Lys Lys Val Cys Leu
Ser Gly Ala Pro His Glu Val Gly Trp Lys 165 170 175 tac cag gca gtg
aca gcc acc ctg gag gaa aag agg aaa gag aaa gcc 576 Tyr Gln Ala Val
Thr Ala Thr Leu Glu Glu Lys Arg Lys Glu Lys Ala 180 185 190 gag atc
cac tac cgg aag aat aaa cag ctc atg agg cta cag aaa cag 624 Glu Ile
His Tyr Arg Lys Asn Lys Gln Leu Met Arg Leu Gln Lys Gln 195 200 205
gcc gag aag aac atg aag aag aaa att gac aaa tac aca gag agt cca 672
Ala Glu Lys Asn Met Lys Lys Lys Ile Asp Lys Tyr Thr Glu Ser Pro 210
215 220 gga gga ggc agt ccc cgt ggc tta ggc ttt atc ttt aag aca ata
gcg 720 Gly Gly Gly Ser Pro Arg Gly Leu Gly Phe Ile Phe Lys Thr Ile
Ala 225 230 235 240 ccg ctc gcc gcc acc cgc gcg act cgg atc ggg cat
ccc ggc ggc cgc 768 Pro Leu Ala Ala Thr Arg Ala Thr Arg Ile Gly His
Pro Gly Gly Arg 245 250 255 acc ccg cgc gct ggc tca tct gca cac cgg
cca cct gca ttg tcg gcc 816 Thr Pro Arg Ala Gly Ser Ser Ala His Arg
Pro Pro Ala Leu Ser Ala 260 265 270 aga gcc ccc gtc ccg gcg gct tcc
cca gca gct tgg ctg ccc ctc agg 864 Arg Ala Pro Val Pro Ala Ala Ser
Pro Ala Ala Trp Leu Pro Leu Arg 275 280 285 acg ccc tgg acc cgc cca
tcc tcc tgc ccc act agc tca tcg act tac 912 Thr Pro Trp Thr Arg Pro
Ser Ser Cys Pro Thr Ser Ser Ser Thr Tyr 290 295 300 gac tcc ctc agt
ccc tac ggc cca cgg aac cct ctc ccc aac ccg cgc 960 Asp Ser Leu Ser
Pro Tyr Gly Pro Arg Asn Pro Leu Pro Asn Pro Arg 305 310 315 320 cac
agc ccg agc ggc ggc ggc ggc ctt aag aag ccc gca aga cac tgt 1008
His Ser Pro Ser Gly Gly Gly Gly Leu Lys Lys Pro Ala Arg His Cys 325
330 335 caa ggt caa aag cac aat gtg cta gcc agg ggg aaa ccc cag aga
aag 1056 Gln Gly Gln Lys His Asn Val Leu Ala Arg Gly Lys Pro Gln
Arg Lys 340 345 350 cca aaa tct gaa aat aac agc tgg tat gta gaa aac
ggc aga cct gct 1104 Pro Lys Ser Glu Asn Asn Ser Trp Tyr Val Glu
Asn Gly Arg Pro Ala 355 360 365 gac ttg gca ggc tca gga tat tgt ggt
gct ctt tgg aag gca ata gag 1152 Asp Leu Ala Gly Ser Gly Tyr Cys
Gly Ala Leu Trp Lys Ala Ile Glu 370 375 380 tcc ttg gag gaa gga ctt
gga gga aaa caa aag gac aag gaa agg aaa 1200 Ser Leu Glu Glu Gly
Leu Gly Gly Lys Gln Lys Asp Lys Glu Arg Lys 385 390 395 400 gca gaa
aat ggc ccc cat cta ctt gtg gaa gca gag caa gcc aag gtg 1248 Ala
Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys Val 405 410
415 ttt tca cac aga ggt ggc aat gtt aca ctg cca tgt aaa ttt tat cga
1296 Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr
Arg 420 425 430 gac cct aca gca ttt ggc tca gga atc cat aaa atc cga
att aag tgg 1344 Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile
Arg Ile Lys Trp 435 440 445 acc aag cta act tcg gat tac ctc aag gaa
gtg gat gtt ttt gtt tcc 1392 Thr Lys Leu Thr Ser Asp Tyr Leu Lys
Glu Val Asp Val Phe Val Ser 450 455 460 atg gga tac cac aaa aaa acc
tat gga ggc tac cag ggt aga gtg ttt 1440 Met Gly Tyr His Lys Lys
Thr Tyr Gly Gly Tyr Gln Gly Arg Val Phe 465 470 475 480 ctg aag gga
ggc agt gat agt gat gct tct ctg gtc atc aca gac ctc 1488 Leu Lys
Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp Leu 485 490 495
act ctg gaa gat tat ggg aga tat aag tgt gag gtg att gaa gga tta
1536 Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly
Leu 500 505 510 gaa gat gat act gtt gtg gta gca ctg gac tta caa ggt
gtg gta ttc 1584 Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln
Gly Val Val Phe 515 520 525 cct tac ttt cca cga ctg ggg cgc tac aat
ctc aat ttt cac gag gcg 1632 Pro Tyr Phe Pro Arg Leu Gly Arg Tyr
Asn Leu Asn Phe His Glu Ala 530 535 540 cag cag gcg tgt ctg gac cag
gat gct gtg atc gcc tcc ttc gac cag 1680 Gln Gln Ala Cys Leu Asp
Gln Asp Ala Val Ile Ala Ser Phe Asp Gln 545 550 555 560 ctg tac gac
gcc tgg cgg ggc ggg ctg gac tgg tgc aat gcc ggc tgg 1728 Leu Tyr
Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly Trp 565 570 575
ctc agt gat ggc tct gtg caa tat ccc atc aca aag ccc aga gag ccc
1776 Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu
Pro 580 585 590 tgt ggg ggg cag aac aca gtg ccc gga gtc agg aac tac
gga ttt tgg 1824 Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn
Tyr Gly Phe Trp 595 600 605 gat aaa gat aaa agc aga tat gat gtt ttc
tgt ttt aca tcc aat ttc 1872 Asp Lys Asp Lys Ser Arg Tyr Asp Val
Phe Cys Phe Thr Ser Asn Phe 610 615 620 aat ggc cgt ttt tac tat ctg
atc cac ccc acc aaa ctg acc tat gat 1920 Asn Gly Arg Phe Tyr Tyr
Leu Ile His Pro Thr Lys Leu Thr Tyr Asp 625 630 635 640 gaa gcg gtg
caa gct tgt ctc aat gat ggt gct cag att gca aaa gtg 1968 Glu Ala
Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys Val 645 650 655
ggc cag ata ttt gct gcc tgg aaa att ctc gga tat gac cgc tgt gat
2016 Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys
Asp 660 665 670 gcg ggc tgg ttg gcg gat ggc agc gtc cgc tac ccc atc
tct agg cca 2064 Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro
Ile Ser Arg Pro 675 680 685 aga agg cgc tgc agt cct act gag gct gca
gtg cgc ttc gtg ggt ttc 2112 Arg Arg Arg Cys Ser Pro Thr Glu Ala
Ala Val Arg Phe Val Gly Phe 690 695 700 cca gat aaa aag cat aag ctg
tat ggt gtc tac tgc ttc aga gca tac 2160 Pro Asp Lys Lys His Lys
Leu Tyr Gly Val Tyr Cys Phe Arg Ala Tyr 705 710 715 720 aac tga
2166 Asn * 5 721 PRT Homo sapiens 5 Met Leu Glu His Thr Thr Lys Thr
Phe Pro Leu Arg Ala Leu His Ile 1 5 10 15 Val Val Glu Ser Ile Arg
Asp His Ser Gly Gln Lys Met Lys Gln Asp 20 25 30 Lys Lys Val Asp
Leu Leu Val Pro Thr Lys Val Thr Gly Ile Ile Thr 35 40 45 Gln Gly
Ala Lys Asp Phe Gly His Val Gln Phe Val Gly Ser Tyr Lys 50 55 60
Leu Ala Tyr Ser Asn Asp Gly Glu His Trp Thr Val Tyr Gln Asp Glu 65
70 75 80 Lys Gln Arg Lys Asp Lys Val Leu Leu Gly Arg Lys Ala Val
Val Val 85 90 95 Ser Cys Glu Gly Ile Asn Ile Ser Gly Ser Phe
Cys
Arg Asn Lys Leu 100 105 110 Lys Tyr Leu Ala Phe Leu His Lys Arg Met
Asn Thr Asn Pro Ser Arg 115 120 125 Arg Pro Tyr His Phe Gln Val Pro
Ser Arg Ile Phe Trp Arg Gln Glu 130 135 140 Lys Ala Asp Gly Gly Ser
Cys Cys Pro Gln Gly His Ala Ser Glu Ala 145 150 155 160 Tyr Lys Lys
Val Cys Leu Ser Gly Ala Pro His Glu Val Gly Trp Lys 165 170 175 Tyr
Gln Ala Val Thr Ala Thr Leu Glu Glu Lys Arg Lys Glu Lys Ala 180 185
190 Glu Ile His Tyr Arg Lys Asn Lys Gln Leu Met Arg Leu Gln Lys Gln
195 200 205 Ala Glu Lys Asn Met Lys Lys Lys Ile Asp Lys Tyr Thr Glu
Ser Pro 210 215 220 Gly Gly Gly Ser Pro Arg Gly Leu Gly Phe Ile Phe
Lys Thr Ile Ala 225 230 235 240 Pro Leu Ala Ala Thr Arg Ala Thr Arg
Ile Gly His Pro Gly Gly Arg 245 250 255 Thr Pro Arg Ala Gly Ser Ser
Ala His Arg Pro Pro Ala Leu Ser Ala 260 265 270 Arg Ala Pro Val Pro
Ala Ala Ser Pro Ala Ala Trp Leu Pro Leu Arg 275 280 285 Thr Pro Trp
Thr Arg Pro Ser Ser Cys Pro Thr Ser Ser Ser Thr Tyr 290 295 300 Asp
Ser Leu Ser Pro Tyr Gly Pro Arg Asn Pro Leu Pro Asn Pro Arg 305 310
315 320 His Ser Pro Ser Gly Gly Gly Gly Leu Lys Lys Pro Ala Arg His
Cys 325 330 335 Gln Gly Gln Lys His Asn Val Leu Ala Arg Gly Lys Pro
Gln Arg Lys 340 345 350 Pro Lys Ser Glu Asn Asn Ser Trp Tyr Val Glu
Asn Gly Arg Pro Ala 355 360 365 Asp Leu Ala Gly Ser Gly Tyr Cys Gly
Ala Leu Trp Lys Ala Ile Glu 370 375 380 Ser Leu Glu Glu Gly Leu Gly
Gly Lys Gln Lys Asp Lys Glu Arg Lys 385 390 395 400 Ala Glu Asn Gly
Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys Val 405 410 415 Phe Ser
His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr Arg 420 425 430
Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys Trp 435
440 445 Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val
Ser 450 455 460 Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly
Arg Val Phe 465 470 475 480 Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser
Leu Val Ile Thr Asp Leu 485 490 495 Thr Leu Glu Asp Tyr Gly Arg Tyr
Lys Cys Glu Val Ile Glu Gly Leu 500 505 510 Glu Asp Asp Thr Val Val
Val Ala Leu Asp Leu Gln Gly Val Val Phe 515 520 525 Pro Tyr Phe Pro
Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu Ala 530 535 540 Gln Gln
Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp Gln 545 550 555
560 Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly Trp
565 570 575 Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg
Glu Pro 580 585 590 Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn
Tyr Gly Phe Trp 595 600 605 Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe
Cys Phe Thr Ser Asn Phe 610 615 620 Asn Gly Arg Phe Tyr Tyr Leu Ile
His Pro Thr Lys Leu Thr Tyr Asp 625 630 635 640 Glu Ala Val Gln Ala
Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys Val 645 650 655 Gly Gln Ile
Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys Asp 660 665 670 Ala
Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg Pro 675 680
685 Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly Phe
690 695 700 Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg
Ala Tyr 705 710 715 720 Asn 6 1957 DNA Homo sapiens CDS
(316)...(1380) 6 ttaggctgta attaggggat ttgggaggag aactttcctg
gtgacgcttt gcttttcttc 60 tgctcttggt gagaaagtgc ctccttcttc
ccaggatcag gacctctgcc atccagcgcc 120 acaaagagac attctgcaca
cacactcaca cacgcacaca cacacacact ctcacactcg 180 cccagagaca
aacttaaggt gaggagaaag agcgctacgt tcacttgatc tccagcttcc 240
aacttaagca gaacttgaga gcatccgaac tcctggattt caggacaagt gaagaagatt
300 ctttgggcta taaag atg aag agt cta ctt ctt ctg gtg ctg att tca
atc 351 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile 1 5 10 tgc
tgg gct gat cat ctt tca gac aac tat act ctg gat cat gac aga 399 Cys
Trp Ala Asp His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg 15 20
25 gct att cac atc caa gca gaa aat ggc ccc cat cta ctt gtg gaa gca
447 Ala Ile His Ile Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala
30 35 40 gag caa gcc aag gtg ttt tca cac aga ggt ggc aat gtt aca
ctg cca 495 Glu Gln Ala Lys Val Phe Ser His Arg Gly Gly Asn Val Thr
Leu Pro 45 50 55 60 tgt aaa ttt tat cga gac cct aca gca ttt ggc tca
gga atc cat aaa 543 Cys Lys Phe Tyr Arg Asp Pro Thr Ala Phe Gly Ser
Gly Ile His Lys 65 70 75 atc cga att aag tgg acc aag cta act tcg
gat tac ctc aag gaa gtg 591 Ile Arg Ile Lys Trp Thr Lys Leu Thr Ser
Asp Tyr Leu Lys Glu Val 80 85 90 gat gtt ttt gtt tcc atg gga tac
cac aaa aaa acc tat gga ggc tac 639 Asp Val Phe Val Ser Met Gly Tyr
His Lys Lys Thr Tyr Gly Gly Tyr 95 100 105 cag ggt aga gtg ttt ctg
aag gga ggc agt gat agt gat gct tct ctg 687 Gln Gly Arg Val Phe Leu
Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu 110 115 120 gtc atc aca gac
ctc act ctg gaa gat tat ggg aga tat aag tgt gag 735 Val Ile Thr Asp
Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu 125 130 135 140 gtg
att gaa gga tta gaa gat gat act gtt gtg gta gca ctg gac tta 783 Val
Ile Glu Gly Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu 145 150
155 caa ggt gtg gta ttc cct tac ttt cca cga ctg ggg cgc tac aat ctc
831 Gln Gly Val Val Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu
160 165 170 aat ttt cac gag gcg cag cag gcg tgt ctg gac cag gat gct
gtg atc 879 Asn Phe His Glu Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala
Val Ile 175 180 185 gcc tcc ttc gac cag ctg tac gac gcc tgg cgg ggc
ggg ctg gac tgg 927 Ala Ser Phe Asp Gln Leu Tyr Asp Ala Trp Arg Gly
Gly Leu Asp Trp 190 195 200 tgc aat gcc ggc tgg ctc agt gat ggc tct
gtg caa tat ccc atc aca 975 Cys Asn Ala Gly Trp Leu Ser Asp Gly Ser
Val Gln Tyr Pro Ile Thr 205 210 215 220 aag ccc aga gag ccc tgt ggg
ggc cag aac aca gtg ccc gga gtc agg 1023 Lys Pro Arg Glu Pro Cys
Gly Gly Gln Asn Thr Val Pro Gly Val Arg 225 230 235 aac tac gga ttt
tgg gat aaa gat aaa agc aga tat gat gtt ttc tgt 1071 Asn Tyr Gly
Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys 240 245 250 ttt
aca tcc aat ttc aat ggc cgt ttt tac tat ctg atc cac ccc acc 1119
Phe Thr Ser Asn Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr 255
260 265 aaa ctg acc tat gat gaa gcg gtg caa gct tgt ctc aat gat ggt
gct 1167 Lys Leu Thr Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn Asp
Gly Ala 270 275 280 cag att gca aaa gtg ggc cag ata ttt gct gcc tgg
aaa att ctc gga 1215 Gln Ile Ala Lys Val Gly Gln Ile Phe Ala Ala
Trp Lys Ile Leu Gly 285 290 295 300 tat gac cgc tgt gat gcg ggc tgg
ttg gcg gat ggc agc gtc cgc tac 1263 Tyr Asp Arg Cys Asp Ala Gly
Trp Leu Ala Asp Gly Ser Val Arg Tyr 305 310 315 ccc atc tct agg cca
aga agg cgc tgc agt cct act gag gct gca gtg 1311 Pro Ile Ser Arg
Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val 320 325 330 cgc ttc
gtg ggt ttc cca gat aaa aag cat aag ctg tat ggt gtc tac 1359 Arg
Phe Val Gly Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr 335 340
345 tgc ttc aga gca tac aac tga atgtgccctt agagcgcatc agttttaaag
1410 Cys Phe Arg Ala Tyr Asn * 350 tcattaagaa catgtgaaag gtgttttttt
tttccaatat gaactcatgc aagttaccaa 1470 aactgtgata accctttttt
acttactgta aagagtcatt ttcataagat caattcattg 1530 atttgttttt
tgtaaagcta tcattcaata tatattataa attaatataa atttaaggga 1590
agctctatgt aaggagactt agagccaaac tgtttaagct gtatcatccc aacaaagtat
1650 cctttcatga acggggcatg caatagctta agaattgcta ggattaaatt
aaggaaagta 1710 aagctactca gagcaacagg ttccacaagc acaaacttta
cacatttgta caattttgaa 1770 atgcactaca ataaacaaat tagagcaaca
catttgaaat acaggcttct ttacataaac 1830 tgagaggtta tacaaaactc
agtttcacaa gggaacaatc tatacctttc taaaagttaa 1890 tatttcaagt
ctctaatagg cagaatattt tactctttaa aatcctgcct ttctgaccaa 1950 aaaaaaa
1957 7 354 PRT Homo sapiens 7 Met Lys Ser Leu Leu Leu Leu Val Leu
Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr
Leu Asp His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly
Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser
His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg
Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70
75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe
Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln
Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser
Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr
Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr Val Val
Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr Phe
Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln
Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190
Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195
200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg
Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn
Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val
Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu
Ile His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala
Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile
Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala
Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315
320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly
325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe
Arg Ala 340 345 350 Tyr Asn 8 1957 DNA Homo sapiens CDS
(316)...(1380) 8 ttaggctgta attaggggat ttgggaggag aactttcctg
gtgacgcttt gcttttcttc 60 tgctcttggt gagaaagtgc ctccttcttc
ccaggatcag gacctctgcc atccagcgcc 120 acaaagagac attctgcaca
cacactcaca cacacacaca cacacacact ctcacactcg 180 cccagagaca
aacttaaggt gaggagaaag agcgctaggt tcacttgatc tccagcttcc 240
aacttaagca gaacttgaga gcatccgaac tcctggattt caggacaagt gaagaagatt
300 ctttgggcta taaag atg aag agt cta ctt ctt ctg gtg ctg att tca
atc 351 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile 1 5 10 tgc
tgg gct gat cat ctt tca gac aac tat act ctg gat cat gac aga 399 Cys
Trp Ala Asp His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg 15 20
25 gct att cac atc caa gca gaa aat ggc ccc cat cta ctt gtg gaa gca
447 Ala Ile His Ile Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala
30 35 40 gag caa gcc aag gtg ttt tca cac aga ggt ggc aat gtt aca
ctg cca 495 Glu Gln Ala Lys Val Phe Ser His Arg Gly Gly Asn Val Thr
Leu Pro 45 50 55 60 tgt aaa ttt tat cga gac cct aca gca ttt ggc tca
gga atc cat aaa 543 Cys Lys Phe Tyr Arg Asp Pro Thr Ala Phe Gly Ser
Gly Ile His Lys 65 70 75 atc cga att aag tgg acc aag cta act tcg
gat tac ctc aag gaa gtg 591 Ile Arg Ile Lys Trp Thr Lys Leu Thr Ser
Asp Tyr Leu Lys Glu Val 80 85 90 gat gtt ttt gtt tcc atg gga tac
cac aaa aaa acc tat gga ggc tac 639 Asp Val Phe Val Ser Met Gly Tyr
His Lys Lys Thr Tyr Gly Gly Tyr 95 100 105 cag ggt aga gtg ttt ctg
aag gga ggc agt gat agt gat gct tct ctg 687 Gln Gly Arg Val Phe Leu
Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu 110 115 120 gtc atc aca gac
ctc act ctg gaa gat tat ggg aga tat aag tgt gag 735 Val Ile Thr Asp
Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu 125 130 135 140 gtg
att gaa gga tta gaa gat gat act gtt gtg gta gca ctg gac tta 783 Val
Ile Glu Gly Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu 145 150
155 caa ggt gtg gta ttc cct tac ttt cca cga ctg ggg cgc tac aat ctc
831 Gln Gly Val Val Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu
160 165 170 aat ttt cac gag gcg cag cag gcg tgt ctg gac cag gat gct
gtg atc 879 Asn Phe His Glu Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala
Val Ile 175 180 185 gcc tcc ttc gac cag ctg tac gac gcc tgg cgg ggc
ggg ctg gac tgg 927 Ala Ser Phe Asp Gln Leu Tyr Asp Ala Trp Arg Gly
Gly Leu Asp Trp 190 195 200 tgc aat gcc ggc tgg ctc agt gat ggc tct
gtg caa tat ccc atc aca 975 Cys Asn Ala Gly Trp Leu Ser Asp Gly Ser
Val Gln Tyr Pro Ile Thr 205 210 215 220 aag ccc aga gag ccc tgt ggg
ggc cag aac aca gtg ccc gga gtc agg 1023 Lys Pro Arg Glu Pro Cys
Gly Gly Gln Asn Thr Val Pro Gly Val Arg 225 230 235 aac tac gga ttt
tgg gat aaa gat aaa agc aga tat gat gtt ttc tgt 1071 Asn Tyr Gly
Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys 240 245 250 ttt
aca tcc aat ttc aat ggc cgt ttt tac tat ctg atc cac ccc acc 1119
Phe Thr Ser Asn Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr 255
260 265 aaa ctg acc tat gat gaa gcg gtg caa gct tgt ctc aat gat ggt
gct 1167 Lys Leu Thr Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn Asp
Gly Ala 270 275 280 cag att gca aaa gtg ggc cag ata ttt gct gcc tgg
aaa att ctc gga 1215 Gln Ile Ala Lys Val Gly Gln Ile Phe Ala Ala
Trp Lys Ile Leu Gly 285 290 295 300 tat gac cgc tgt gat gcg ggc tgg
ttg gcg gat ggc agc gtc cgc tac 1263 Tyr Asp Arg Cys Asp Ala Gly
Trp Leu Ala Asp Gly Ser Val Arg Tyr 305 310 315 ccc atc tct agg cca
aga agg cgc tgc agt cct act gag gct gca gtg 1311 Pro Ile Ser Arg
Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val 320 325 330 cgc ttc
gtg ggt ttc cca gat aaa aag cat aag ctg tat ggt gtc tac 1359 Arg
Phe Val Gly Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr 335 340
345 tgc ttc aga gca tac aac tga atgtgccctt agagcgcatc agttttaaag
1410 Cys Phe Arg Ala Tyr Asn * 350 tcattaagaa catgtgaaag gtgttttttt
tttccaatat gaactcatgc aagttaccaa 1470 aactgtgata accctttttt
acttactgta aagagtcatt ttcataagat caattcattg 1530 atttgttttt
tgtaaagcta tcattcaata tatattataa attaatataa atttaaggga 1590
agctctatgt aaggagactt agagccaaac tgtttaagct gtatcatccc aacaaagtat
1650 cctttcatga acggggcatg caatagctta agaattgcta ggattaaatt
aaggaaagta 1710 aagctactca gagcaacagg ttccacaagc acaaacttta
cacatttgta caattttgaa 1770 atgcactaca ataaacaaat tagagcaaca
catttgaaat acaggcttct ttacataaac 1830 tgagaggtta tacaaaactc
agtttcacaa gggaacaatc tatacctttc taaaagttaa 1890 tatttcaagt
ctctaatagg cagaatattt tactctttaa aatcctgcct ttctgaccaa 1950 aaaaaaa
1957 9 354 PRT Homo sapiens 9 Met Lys Ser Leu Leu Leu Leu Val Leu
Ile
Ser Ile Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu
Asp His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro
His Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His
Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp
Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80
Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85
90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg
Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val
Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys
Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr Val Val Val Ala
Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg
Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala
Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu
Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205
Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210
215 220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly
Phe 225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys
Phe Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His
Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu
Asn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala
Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp
Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro
Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330
335 Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala
340 345 350 Tyr Asn 10 1957 DNA Homo sapiens CDS (316)...(1380) 10
ttaggctgta attaggggat ttgggaggag aactttcctg gtgacgcttt gcttttcttc
60 tgctcttggt gagaaagtgc ctccttcttc ccaggatcag gacctctgcc
atccagcgcc 120 acaaagagac attctgcaca cacactcaca cacacacaca
cacacacact ctcacactcg 180 cccagagaca aacttaaggt gaggagaaag
agcgctacct tcacttgatc tccagcttcc 240 aacttaagca gaacttgaga
gcatccgaac tcctggattt caggacaagt gaagaagatt 300 ctttgggcta taaag
atg aag agt cta ctt ctt ctg gtg ctg att tca atc 351 Met Lys Ser Leu
Leu Leu Leu Val Leu Ile Ser Ile 1 5 10 tgc tgg gct gat cat ctt tca
gac aac tat act ctg gat cat gac aga 399 Cys Trp Ala Asp His Leu Ser
Asp Asn Tyr Thr Leu Asp His Asp Arg 15 20 25 gct att cac atc caa
gca gaa aat ggc ccc cat cta ctt gtg gaa gca 447 Ala Ile His Ile Gln
Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala 30 35 40 gag caa gcc
aag gtg ttt tca cac aga ggt ggc aat gtt aca ctg cca 495 Glu Gln Ala
Lys Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro 45 50 55 60 tgt
aaa ttt tat cga gac cct aca gca ttt ggc tca gga atc cat aaa 543 Cys
Lys Phe Tyr Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys 65 70
75 atc cga att aag tgg acc aag cta act tcg gat tac ctc aag gaa gtg
591 Ile Arg Ile Lys Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val
80 85 90 gat gtt ttt gtt tcc atg gga tac cac aaa aaa acc tat gga
ggc tac 639 Asp Val Phe Val Ser Met Gly Tyr His Lys Lys Thr Tyr Gly
Gly Tyr 95 100 105 cag ggt aga gtg ttt ctg aag gga ggc agt gat agt
gat gct tct ctg 687 Gln Gly Arg Val Phe Leu Lys Gly Gly Ser Asp Ser
Asp Ala Ser Leu 110 115 120 gtc atc aca gac ctc act ctg gaa gat tat
ggg aga tat aag tgt gag 735 Val Ile Thr Asp Leu Thr Leu Glu Asp Tyr
Gly Arg Tyr Lys Cys Glu 125 130 135 140 gtg att gaa gga tta gaa gat
gat act gtt gtg gta gca ctg gac tta 783 Val Ile Glu Gly Leu Glu Asp
Asp Thr Val Val Val Ala Leu Asp Leu 145 150 155 caa ggt gtg gta ttc
cct tac ttt cca cga ctg ggg cgc tac aat ctc 831 Gln Gly Val Val Phe
Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu 160 165 170 aat ttt cac
gag gcg cag cag gcg tgt ctg gac cag gat gct gtg atc 879 Asn Phe His
Glu Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile 175 180 185 gcc
tcc ttc gac cag ctg tac gac gcc tgg cgg ggc ggg ctg gac tgg 927 Ala
Ser Phe Asp Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp 190 195
200 tgc aat gcc ggc tgg ctc agt gat ggc tct gtg caa tat ccc atc aca
975 Cys Asn Ala Gly Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr
205 210 215 220 aag ccc aga gag ccc tgt ggg ggc cag aac aca gtg ccc
gga gtc agg 1023 Lys Pro Arg Glu Pro Cys Gly Gly Gln Asn Thr Val
Pro Gly Val Arg 225 230 235 aac tac gga ttt tgg gat aaa gat aaa agc
aga tat gat gtt ttc tgt 1071 Asn Tyr Gly Phe Trp Asp Lys Asp Lys
Ser Arg Tyr Asp Val Phe Cys 240 245 250 ttt aca tcc aat ttc aat ggc
cgt ttt tac tat ctg atc cac ccc acc 1119 Phe Thr Ser Asn Phe Asn
Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr 255 260 265 aaa ctg acc tat
gat gaa gcg gtg caa gct tgt ctc aat gat ggt gct 1167 Lys Leu Thr
Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala 270 275 280 cag
att gca aaa gtg ggc cag ata ttt gct gcc tgg aaa att ctc gga 1215
Gln Ile Ala Lys Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly 285
290 295 300 tat gac cgc tgt gat gcg ggc tgg ttg gcg gat ggc agc gtc
cgc tac 1263 Tyr Asp Arg Cys Asp Ala Gly Trp Leu Ala Asp Gly Ser
Val Arg Tyr 305 310 315 ccc atc tct agg cca aga agg cgc tgc agt cct
act gag gct gca gtg 1311 Pro Ile Ser Arg Pro Arg Arg Arg Cys Ser
Pro Thr Glu Ala Ala Val 320 325 330 cgc ttc gtg ggt ttc cca gat aaa
aag cat aag ctg tat ggt gtc tac 1359 Arg Phe Val Gly Phe Pro Asp
Lys Lys His Lys Leu Tyr Gly Val Tyr 335 340 345 tgc ttc aga gca tac
aac tga atgtgccctt agagcgcatc agttttaaag 1410 Cys Phe Arg Ala Tyr
Asn * 350 tcattaagaa catgtgaaag gtgttttttt tttccaatat gaactcatgc
aagttaccaa 1470 aactgtgata accctttttt acttactgta aagagtcatt
ttcataagat caattcattg 1530 atttgttttt tgtaaagcta tcattcaata
tatattataa attaatataa atttaaggga 1590 agctctatgt aaggagactt
agagccaaac tgtttaagct gtatcatccc aacaaagtat 1650 cctttcatga
acggggcatg caatagctta agaattgcta ggattaaatt aaggaaagta 1710
aagctactca gagcaacagg ttccacaagc acaaacttta cacatttgta caattttgaa
1770 atgcactaca ataaacaaat tagagcaaca catttgaaat acaggcttct
ttacataaac 1830 tgagaggtta tacaaaactc agtttcacaa gggaacaatc
tatacctttc taaaagttaa 1890 tatttcaagt ctctaatagg cagaatattt
tactctttaa aatcctgcct ttctgaccaa 1950 aaaaaaa 1957 11 354 PRT Homo
sapiens 11 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile Cys Trp
Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg
Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu Val
Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn
Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe
Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu
Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90 95 Ser Met
Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110
Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115
120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu
Gly 130 135 140 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln
Gly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr
Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln
Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp
Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp
Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys
Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235
240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn
245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu
Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala
Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile
Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly
Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys
Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe Pro Asp
Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr
Asn 12 1957 DNA Homo sapiens CDS (316)...(1380) 12 ttaggctgta
attaggggat ttgggaggag aactttcctg gtgacgcttt gcttttcttc 60
tgctcttggt gagaaagtgc ctccttcttc ccaggatcag gacctctgcc atccagcgcc
120 acaaagagac attctgcaca cacactcaca cacacacaca cacacacact
ctcacactcg 180 cccagagaca aacttaaggt gaggagaaag agcgctacgt
tcacttgatc tccagcttcc 240 aacttaagca gaacttgaga gcatccgaac
tcctggattt caggacaagt gaagaagatt 300 ctttgggcta taaag atg aag agt
cta ctt ctt ctg gtg ctg att tca atc 351 Met Lys Ser Leu Leu Leu Leu
Val Leu Ile Ser Ile 1 5 10 tgc tgg gct gat cat ctt tca gac aac tat
act ctg gat cat gac aga 399 Cys Trp Ala Asp His Leu Ser Asp Asn Tyr
Thr Leu Asp His Asp Arg 15 20 25 gct att cac atc caa gca gaa aat
ggc ccc cat cta ctt gtg gaa gca 447 Ala Ile His Ile Gln Ala Glu Asn
Gly Pro His Leu Leu Val Glu Ala 30 35 40 gag caa gcc aag gtg ttt
tca cac aga ggt ggc aat gtt aca ctg cca 495 Glu Gln Ala Lys Val Phe
Ser His Arg Gly Gly Asn Val Thr Leu Pro 45 50 55 60 tgt aaa ttt tat
cga gac cct aca gca ttt ggc tca gga atc cat aaa 543 Cys Lys Phe Tyr
Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys 65 70 75 atc cga
att aag tgg acc aag cta act tcg gat tac ctc aag gaa gtg 591 Ile Arg
Ile Lys Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val 80 85 90
gat gtt ttt gtt tcc atg gga tac cac aaa aaa acc tat gga ggc tac 639
Asp Val Phe Val Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr 95
100 105 cag ggt aga gtg ttt ctg aag gga ggc agt gat agt gat gct tct
ctg 687 Gln Gly Arg Val Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser
Leu 110 115 120 gtc atc aca gac ctc act ctg gaa gat tat ggg aga tat
aag tgt gag 735 Val Ile Thr Asp Leu Thr Leu Glu Asp Tyr Gly Arg Tyr
Lys Cys Glu 125 130 135 140 gtg att gaa gga tta gaa gat gat act gtt
gtg gta gca ctg gac tta 783 Val Ile Glu Gly Leu Glu Asp Asp Thr Val
Val Val Ala Leu Asp Leu 145 150 155 caa ggt gtg gta ttc cct tac ttt
cca cga ctg ggg cgc tac aat ctc 831 Gln Gly Val Val Phe Pro Tyr Phe
Pro Arg Leu Gly Arg Tyr Asn Leu 160 165 170 aat ttt cac gag gcg cag
cag gcg tgt ctg gac cag gat gct gtg atc 879 Asn Phe His Glu Ala Gln
Gln Ala Cys Leu Asp Gln Asp Ala Val Ile 175 180 185 gcc tcc ttc gac
cag ctg tac gac gcc tgg cgg ggc ggg ctg gac tgg 927 Ala Ser Phe Asp
Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp 190 195 200 tgc aat
gcc ggc tgg ctc agt gat ggc tct gtg caa tat ccc atc aca 975 Cys Asn
Ala Gly Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr 205 210 215
220 aag ccc aga gag ccc tgt ggg ggg cag aac aca gtg ccc gga gtc agg
1023 Lys Pro Arg Glu Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val
Arg 225 230 235 aac tac gga ttt tgg gat aaa gat aaa agc aga tat gat
gtt ttc tgt 1071 Asn Tyr Gly Phe Trp Asp Lys Asp Lys Ser Arg Tyr
Asp Val Phe Cys 240 245 250 ttt aca tcc aat ttc aat ggc cgt ttt tac
tat ctg atc cac ccc acc 1119 Phe Thr Ser Asn Phe Asn Gly Arg Phe
Tyr Tyr Leu Ile His Pro Thr 255 260 265 aaa ctg acc tat gat gaa gcg
gtg caa gct tgt ctc aat gat ggt gct 1167 Lys Leu Thr Tyr Asp Glu
Ala Val Gln Ala Cys Leu Asn Asp Gly Ala 270 275 280 cag att gca aaa
gtg ggc cag ata ttt gct gcc tgg aaa att ctc gga 1215 Gln Ile Ala
Lys Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly 285 290 295 300
tat gac cgc tgt gat gcg ggc tgg ttg gcg gat ggc agc gtc cgc tac
1263 Tyr Asp Arg Cys Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg
Tyr 305 310 315 ccc atc tct agg cca aga agg cgc tgc agt cct act gag
gct gca gtg 1311 Pro Ile Ser Arg Pro Arg Arg Arg Cys Ser Pro Thr
Glu Ala Ala Val 320 325 330 cgc ttc gtg ggt ttc cca gat aaa aag cat
aag ctg tat ggt gtc tac 1359 Arg Phe Val Gly Phe Pro Asp Lys Lys
His Lys Leu Tyr Gly Val Tyr 335 340 345 tgc ttc aga gca tac aac tga
atgtgccctt agagcgcatc agttttaaag 1410 Cys Phe Arg Ala Tyr Asn * 350
tcattaagaa catgtgaaag gtgttttttt tttccaatat gaactcatgc aagttaccaa
1470 aactgtgata accctttttt acttactgta aagagtcatt ttcataagat
caattcattg 1530 atttgttttt tgtaaagcta tcattcaata tatattataa
attaatataa atttaaggga 1590 agctctatgt aaggagactt agagccaaac
tgtttaagct gtatcatccc aacaaagtat 1650 cctttcatga acggggcatg
caatagctta agaattgcta ggattaaatt aaggaaagta 1710 aagctactca
gagcaacagg ttccacaagc acaaacttta cacatttgta caattttgaa 1770
atgcactaca ataaacaaat tagagcaaca catttgaaat acaggcttct ttacataaac
1830 tgagaggtta tacaaaactc agtttcacaa gggaacaatc tatacctttc
taaaagttaa 1890 tatttcaagt ctctaatagg cagaatattt tactctttaa
aatcctgcct ttctgaccaa 1950 aaaaaaa 1957 13 354 PRT Homo sapiens 13
Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 5
10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His
Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu
Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu
Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly
Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp
Tyr Leu Lys Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His
Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys
Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu
Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135
140 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val
145 150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn
Phe His Glu 165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val
Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly
Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val
Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln
Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235 240 Trp Asp
Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250 255
Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr
260
265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala
Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr
Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg
Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr
Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His
Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 14 1957
DNA Homo sapiens CDS (316)...(1380) 14 ttaggctgta attaggggat
ttgggaggag aactttcctg gtgacgcttt gcttttcttc 60 tgctcttggt
gagaaagtgc ctccttcttc ccaggatcag gacctctgcc atccagcgcc 120
acaaagagac attctgcaca cacactcaca cacacacaca cacacacact ctcacactcg
180 cccagagaca aacttaaggt gaggagaaag agcgctacgt tcacttgatc
tccagcttcc 240 aacttaagca gaacttgaga gcatccgaac tcctggattt
caggacaagt gaagaagatt 300 ctttgggcta taaag atg aag agt cta ctt ctt
ctg gtg ctg att tca atc 351 Met Lys Ser Leu Leu Leu Leu Val Leu Ile
Ser Ile 1 5 10 tgc tgg gct gat cat ctt tca gac aac tat act ctg gat
cat gac aga 399 Cys Trp Ala Asp His Leu Ser Asp Asn Tyr Thr Leu Asp
His Asp Arg 15 20 25 gct att cac atc caa gca gaa aat ggc ccc cat
cta ctt gtg gaa gca 447 Ala Ile His Ile Gln Ala Glu Asn Gly Pro His
Leu Leu Val Glu Ala 30 35 40 gag caa gcc aag gtg ttt tca cac aga
ggt ggc aat gtt aca ctg cca 495 Glu Gln Ala Lys Val Phe Ser His Arg
Gly Gly Asn Val Thr Leu Pro 45 50 55 60 tgt aaa ttt tat cga gac cct
aca gca ttt ggc tca gga atc cat aaa 543 Cys Lys Phe Tyr Arg Asp Pro
Thr Ala Phe Gly Ser Gly Ile His Lys 65 70 75 atc cga att aag tgg
acc aag cta act tcg gat tac ctc aag gaa gtg 591 Ile Arg Ile Lys Trp
Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val 80 85 90 gat gtt ttt
gtt tcc atg gga tac cac aaa aaa acc tat gga ggc tac 639 Asp Val Phe
Val Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr 95 100 105 cag
ggt aga gtg ttt ctg aag gga ggc agt gat agt gat gct tct ctg 687 Gln
Gly Arg Val Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu 110 115
120 gtc atc aca gac ctc act ctg gaa gat tat ggg aga tat aag tgt gag
735 Val Ile Thr Asp Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu
125 130 135 140 gtg att gaa gga tta gaa gat gat act gtt gtg gta gca
ctg gac tta 783 Val Ile Glu Gly Leu Glu Asp Asp Thr Val Val Val Ala
Leu Asp Leu 145 150 155 caa ggt gtg gta ttc cct tac ttt cca cga ctg
ggg cgc tac aat ctc 831 Gln Gly Val Val Phe Pro Tyr Phe Pro Arg Leu
Gly Arg Tyr Asn Leu 160 165 170 aat ttt cac gag gcg cag cag gcg tgt
ctg gac cag gat gct gtg atc 879 Asn Phe His Glu Ala Gln Gln Ala Cys
Leu Asp Gln Asp Ala Val Ile 175 180 185 gcc tcc ttc gac cag ctg tac
gac gcc tgg cgg ggc ggg ctg gac tgg 927 Ala Ser Phe Asp Gln Leu Tyr
Asp Ala Trp Arg Gly Gly Leu Asp Trp 190 195 200 tgc aat gcc ggc tgg
ctc agt gat ggc tct gtg caa tat ccc atc aca 975 Cys Asn Ala Gly Trp
Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr 205 210 215 220 aag ccc
aga gag ccc tgt ggg ggc cag aac aca gtg ccc gga gtc agg 1023 Lys
Pro Arg Glu Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg 225 230
235 aac tac gga ttt tgg gat aaa gat aaa agc aga tat gat gtt ttc tgt
1071 Asn Tyr Gly Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe
Cys 240 245 250 ttt aca tcc aat ttc aat ggc cgt ttt tac tat ctg atc
cac ccc acc 1119 Phe Thr Ser Asn Phe Asn Gly Arg Phe Tyr Tyr Leu
Ile His Pro Thr 255 260 265 aaa ctg acc tat gat gaa gcg gtg caa gct
tgt ctc aat gat ggt gct 1167 Lys Leu Thr Tyr Asp Glu Ala Val Gln
Ala Cys Leu Asn Asp Gly Ala 270 275 280 cag att gca aaa gtg ggc cag
ata ttt gct gcc tgg aaa att ctc gga 1215 Gln Ile Ala Lys Val Gly
Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly 285 290 295 300 tat gac cgc
tgt gat gcg ggc tgg ttg gcg gat ggc agc gtc cgc tac 1263 Tyr Asp
Arg Cys Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr 305 310 315
ccc atc tct agg cca aga agg cgc tgc agt cct act gag gct gca gtg
1311 Pro Ile Ser Arg Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala
Val 320 325 330 cgc ttc gtg ggt ttt cca gat aaa aag cat aag ctg tat
ggt gtc tac 1359 Arg Phe Val Gly Phe Pro Asp Lys Lys His Lys Leu
Tyr Gly Val Tyr 335 340 345 tgc ttc aga gca tac aac tga atgtgccctt
agagcgcatc agttttaaag 1410 Cys Phe Arg Ala Tyr Asn * 350 tcattaagaa
catgtgaaag gtgttttttt tttccaatat gaactcatgc aagttaccaa 1470
aactgtgata accctttttt acttactgta aagagtcatt ttcataagat caattcattg
1530 atttgttttt tgtaaagcta tcattcaata tatattataa attaatataa
atttaaggga 1590 agctctatgt aaggagactt agagccaaac tgtttaagct
gtatcatccc aacaaagtat 1650 cctttcatga acggggcatg caatagctta
agaattgcta ggattaaatt aaggaaagta 1710 aagctactca gagcaacagg
ttccacaagc acaaacttta cacatttgta caattttgaa 1770 atgcactaca
ataaacaaat tagagcaaca catttgaaat acaggcttct ttacataaac 1830
tgagaggtta tacaaaactc agtttcacaa gggaacaatc tatacctttc taaaagttaa
1890 tatttcaagt ctctaatagg cagaatattt tactctttaa aatcctgcct
ttctgaccaa 1950 aaaaaaa 1957 15 354 PRT Homo sapiens 15 Met Lys Ser
Leu Leu Leu Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His
Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 20 25
30 Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys
35 40 45 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys
Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys
Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys
Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr
Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser
Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu
Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu
Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155
160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu
165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser
Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp
Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro
Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val
Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys
Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly
Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp
Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275 280
285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys
290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile
Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala
Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr
Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 16 1957 DNA Homo
sapiens CDS (316)...(1380) 16 ttaggctgta attaggggat ttgggaggag
aactttcctg gtgacgcttt gcttttcttc 60 tgctcttggt gagaaagtgc
ctccttcttc ccaggatcag gacctctgcc atccagcgcc 120 acaaagagac
attctgcaca cacactcaca cacacacaca cacacacact ctcacactcg 180
cccagagaca aacttaaggt gaggagaaag agcgctacgt tcacttgatc tccagcttcc
240 aacttaagca gaacttgaga gcatccgaac tcctggattt caggacaagt
gaagaagatt 300 ctttgggcta taaag atg aag agt cta ctt ctt ctg gtg ctg
att tca atc 351 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile 1 5
10 tgc tgg gct gat cat ctt tca gac aac tat act ctg gat cat gac aga
399 Cys Trp Ala Asp His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg
15 20 25 gct att cac atc caa gca gaa aat ggc ccc cat cta ctt gtg
gaa gca 447 Ala Ile His Ile Gln Ala Glu Asn Gly Pro His Leu Leu Val
Glu Ala 30 35 40 gag caa gcc aag gtg ttt tca cac aga ggt ggc aat
gtt aca ctg cca 495 Glu Gln Ala Lys Val Phe Ser His Arg Gly Gly Asn
Val Thr Leu Pro 45 50 55 60 tgt aaa ttt tat cga gac cct aca gca ttt
ggc tca gga atc cat aaa 543 Cys Lys Phe Tyr Arg Asp Pro Thr Ala Phe
Gly Ser Gly Ile His Lys 65 70 75 atc cga att aag tgg acc aag cta
act tcg gat tac ctc aag gaa gtg 591 Ile Arg Ile Lys Trp Thr Lys Leu
Thr Ser Asp Tyr Leu Lys Glu Val 80 85 90 gat gtt ttt gtt tcc atg
gga tac cac aaa aaa acc tat gga ggc tac 639 Asp Val Phe Val Ser Met
Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr 95 100 105 cag ggt aga gtg
ttt ctg aag gga ggc agt gat agt gat gct tct ctg 687 Gln Gly Arg Val
Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu 110 115 120 gtc atc
aca gac ctc act ctg gaa gat tat ggg aga tat aag tgt gag 735 Val Ile
Thr Asp Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu 125 130 135
140 gtg att gaa gga tta gaa gat gat act gtt gtg gta gca ctg gac tta
783 Val Ile Glu Gly Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu
145 150 155 caa ggt gtg gta ttc cct tac ttt cca cga ctg ggg cgc tac
aat ctc 831 Gln Gly Val Val Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr
Asn Leu 160 165 170 aat ttt cac gag gcg cag cag gcg tgt ctg gac cag
gat gct gtg atc 879 Asn Phe His Glu Ala Gln Gln Ala Cys Leu Asp Gln
Asp Ala Val Ile 175 180 185 gcc tcc ttc gac cag ctg tac gac gcc tgg
cgg ggc ggg ctg gac tgg 927 Ala Ser Phe Asp Gln Leu Tyr Asp Ala Trp
Arg Gly Gly Leu Asp Trp 190 195 200 tgc aat gcc ggc tgg ctc agt gat
ggc tct gtg caa tat ccc atc aca 975 Cys Asn Ala Gly Trp Leu Ser Asp
Gly Ser Val Gln Tyr Pro Ile Thr 205 210 215 220 aag ccc aga gag ccc
tgt ggg ggc cag aac aca gtg ccc gga gtc agg 1023 Lys Pro Arg Glu
Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg 225 230 235 aac tac
gga ttt tgg gat aaa gat aaa agc aga tat gat gtt ttc tgt 1071 Asn
Tyr Gly Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys 240 245
250 ttt aca tcc aat ttc aat ggc cgt ttt tac tat ctg atc cac ccc acc
1119 Phe Thr Ser Asn Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro
Thr 255 260 265 aaa ctg acc tat gat gaa gcg gtg caa gct tgt ctc aat
gat ggt gct 1167 Lys Leu Thr Tyr Asp Glu Ala Val Gln Ala Cys Leu
Asn Asp Gly Ala 270 275 280 cag att gca aaa gtg ggc cag ata ttt gct
gcc tgg aaa att ctc gga 1215 Gln Ile Ala Lys Val Gly Gln Ile Phe
Ala Ala Trp Lys Ile Leu Gly 285 290 295 300 tat gac cgc tgt gat gcg
ggc tgg ttg gcg gat ggc agc gtc cgc tac 1263 Tyr Asp Arg Cys Asp
Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr 305 310 315 ccc atc tct
agg cca aga agg cgc tgc agt cct act gag gct gca gtg 1311 Pro Ile
Ser Arg Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val 320 325 330
cgc ttc gtg ggt ttc cca gat aaa aag cat aag ctg tat ggt gtc tac
1359 Arg Phe Val Gly Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val
Tyr 335 340 345 tgc ttc aga gca tac aac tga atgtgccctt agagcgcacc
agttttaaag 1410 Cys Phe Arg Ala Tyr Asn * 350 tcattaagaa catgtgaaag
gtgttttttt tttccaatat gaactcatgc aagttaccaa 1470 aactgtgata
accctttttt acttactgta aagagtcatt ttcataagat caattcattg 1530
atttgttttt tgtaaagcta tcattcaata tatattataa attaatataa atttaaggga
1590 agctctatgt aaggagactt agagccaaac tgtttaagct gtatcatccc
aacaaagtat 1650 cctttcatga acggggcatg caatagctta agaattgcta
ggattaaatt aaggaaagta 1710 aagctactca gagcaacagg ttccacaagc
acaaacttta cacatttgta caattttgaa 1770 atgcactaca ataaacaaat
tagagcaaca catttgaaat acaggcttct ttacataaac 1830 tgagaggtta
tacaaaactc agtttcacaa gggaacaatc tatacctttc taaaagttaa 1890
tatttcaagt ctctaatagg cagaatattt tactctttaa aatcctgcct ttctgaccaa
1950 aaaaaaa 1957 17 354 PRT Homo sapiens 17 Met Lys Ser Leu Leu
Leu Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His Leu Ser
Asp Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 20 25 30 Gln
Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40
45 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr
50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg
Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val
Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly
Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser
Asp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr
Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp
Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe
Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170
175 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp
180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn
Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr
Lys Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly
Val Arg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys Ser Arg
Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe
Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala
Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val
Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295
300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg
305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg
Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val
Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 18 1957 DNA Homo sapiens
CDS (316)...(1380) 18 ttaggctgta attaggggat ttgggaggag aactttcctg
gtgacgcttt gcttttcttc 60 tgctcttggt gagaaagtgc ctccttcttc
ccaggatcag gacctctgcc atccagcgcc 120 acaaagagac attctgcaca
cacactcaca cacacacaca cacacacact ctcacactcg 180 cccagagaca
aacttaaggt gaggagaaag agcgctacgt tcacttgatc tccagcttcc 240
aacttaagca gaacttgaga gcatccgaac tcctggattt caggacaagt gaagaagatt
300 ctttgggcta taaag atg aag agt cta ctt ctt ctg gtg ctg att tca
atc 351 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile 1 5 10 tgc
tgg gct gat cat ctt tca gac aac tat act ctg gat cat gac aga 399 Cys
Trp Ala Asp His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg 15 20
25 gct att cac atc caa gca gaa aat ggc ccc cat cta ctt gtg gaa gca
447 Ala Ile His Ile Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala
30 35 40 gag caa gcc aag gtg ttt tca cac aga ggt ggc aat gtt aca
ctg cca 495 Glu Gln Ala Lys Val Phe Ser His Arg Gly Gly Asn Val Thr
Leu Pro 45 50 55 60 tgt aaa ttt tat cga gac cct aca gca ttt ggc tca
gga atc cat aaa 543 Cys Lys Phe Tyr Arg Asp Pro Thr Ala Phe Gly Ser
Gly Ile His Lys
65 70 75 atc cga att aag tgg acc aag cta act tcg gat tac ctc aag
gaa gtg 591 Ile Arg Ile Lys Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys
Glu Val 80 85 90 gat gtt ttt gtt tcc atg gga tac cac aaa aaa acc
tat gga ggc tac 639 Asp Val Phe Val Ser Met Gly Tyr His Lys Lys Thr
Tyr Gly Gly Tyr 95 100 105 cag ggt aga gtg ttt ctg aag gga ggc agt
gat agt gat gct tct ctg 687 Gln Gly Arg Val Phe Leu Lys Gly Gly Ser
Asp Ser Asp Ala Ser Leu 110 115 120 gtc atc aca gac ctc act ctg gaa
gat tat ggg aga tat aag tgt gag 735 Val Ile Thr Asp Leu Thr Leu Glu
Asp Tyr Gly Arg Tyr Lys Cys Glu 125 130 135 140 gtg att gaa gga tta
gaa gat gat act gtt gtg gta gca ctg gac tta 783 Val Ile Glu Gly Leu
Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu 145 150 155 caa ggt gtg
gta ttc cct tac ttt cca cga ctg ggg cgc tac aat ctc 831 Gln Gly Val
Val Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu 160 165 170 aat
ttt cac gag gcg cag cag gcg tgt ctg gac cag gat gct gtg atc 879 Asn
Phe His Glu Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile 175 180
185 gcc tcc ttc gac cag ctg tac gac gcc tgg cgg ggc ggg ctg gac tgg
927 Ala Ser Phe Asp Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp
190 195 200 tgc aat gcc ggc tgg ctc agt gat ggc tct gtg caa tat ccc
atc aca 975 Cys Asn Ala Gly Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro
Ile Thr 205 210 215 220 aag ccc aga gag ccc tgt ggg ggc cag aac aca
gtg ccc gga gtc agg 1023 Lys Pro Arg Glu Pro Cys Gly Gly Gln Asn
Thr Val Pro Gly Val Arg 225 230 235 aac tac gga ttt tgg gat aaa gat
aaa agc aga tat gat gtt ttc tgt 1071 Asn Tyr Gly Phe Trp Asp Lys
Asp Lys Ser Arg Tyr Asp Val Phe Cys 240 245 250 ttt aca tcc aat ttc
aat ggc cgt ttt tac tat ctg atc cac ccc acc 1119 Phe Thr Ser Asn
Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr 255 260 265 aaa ctg
acc tat gat gaa gcg gtg caa gct tgt ctc aat gat ggt gct 1167 Lys
Leu Thr Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala 270 275
280 cag att gca aaa gtg ggc cag ata ttt gct gcc tgg aaa att ctc gga
1215 Gln Ile Ala Lys Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu
Gly 285 290 295 300 tat gac cgc tgt gat gcg ggc tgg ttg gcg gat ggc
agc gtc cgc tac 1263 Tyr Asp Arg Cys Asp Ala Gly Trp Leu Ala Asp
Gly Ser Val Arg Tyr 305 310 315 ccc atc tct agg cca aga agg cgc tgc
agt cct act gag gct gca gtg 1311 Pro Ile Ser Arg Pro Arg Arg Arg
Cys Ser Pro Thr Glu Ala Ala Val 320 325 330 cgc ttc gtg ggt ttc cca
gat aaa aag cat aag ctg tat ggt gtc tac 1359 Arg Phe Val Gly Phe
Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr 335 340 345 tgc ttc aga
gca tac aac tga atgtgccctt agagcgcatt agttttaaag 1410 Cys Phe Arg
Ala Tyr Asn * 350 tcattaagaa catgtgaaag gtgttttttt tttccaatat
gaactcatgc aagttaccaa 1470 aactgtgata accctttttt acttactgta
aagagtcatt ttcataagat caattcattg 1530 atttgttttt tgtaaagcta
tcattcaata tatattataa attaatataa atttaaggga 1590 agctctatgt
aaggagactt agagccaaac tgtttaagct gtatcatccc aacaaagtat 1650
cctttcatga acggggcatg caatagctta agaattgcta ggattaaatt aaggaaagta
1710 aagctactca gagcaacagg ttccacaagc acaaacttta cacatttgta
caattttgaa 1770 atgcactaca ataaacaaat tagagcaaca catttgaaat
acaggcttct ttacataaac 1830 tgagaggtta tacaaaactc agtttcacaa
gggaacaatc tatacctttc taaaagttaa 1890 tatttcaagt ctctaatagg
cagaatattt tactctttaa aatcctgcct ttctgaccaa 1950 aaaaaaa 1957 19
354 PRT Homo sapiens 19 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser
Ile Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp
His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His
Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg
Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro
Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp
Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90
95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val
100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile
Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu
Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr Val Val Val Ala Leu
Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg Leu
Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys
Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr
Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp
Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215
220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe
225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe
Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro
Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn
Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala
Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu
Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg
Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335
Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340
345 350 Tyr Asn 20 1957 DNA Homo sapiens CDS (316)...(1380) 20
ttaggctgta attaggggat ttgggaggag aactttcctg gtgacgcttt gcttttcttc
60 tgctcttggt gagaaagtgc ctccttcttc ccaggatcag gacctctgcc
atccagcgcc 120 acaaagagac attctgcaca cacactcaca cacacacaca
cacacacact ctcacactcg 180 cccagagaca aacttaaggt gaggagaaag
agcgctacgt tcacttgatc tccagcttcc 240 aacttaagca gaacttgaga
gcatccgaac tcctggattt caggacaagt gaagaagatt 300 ctttgggcta taaag
atg aag agt cta ctt ctt ctg gtg ctg att tca atc 351 Met Lys Ser Leu
Leu Leu Leu Val Leu Ile Ser Ile 1 5 10 tgc tgg gct gat cat ctt tca
gac aac tat act ctg gat cat gac aga 399 Cys Trp Ala Asp His Leu Ser
Asp Asn Tyr Thr Leu Asp His Asp Arg 15 20 25 gct att cac atc caa
gca gaa aat ggc ccc cat cta ctt gtg gaa gca 447 Ala Ile His Ile Gln
Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala 30 35 40 gag caa gcc
aag gtg ttt tca cac aga ggt ggc aat gtt aca ctg cca 495 Glu Gln Ala
Lys Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro 45 50 55 60 tgt
aaa ttt tat cga gac cct aca gca ttt ggc tca gga atc cat aaa 543 Cys
Lys Phe Tyr Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys 65 70
75 atc cga att aag tgg acc aag cta act tcg gat tac ctc aag gaa gtg
591 Ile Arg Ile Lys Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val
80 85 90 gat gtt ttt gtt tcc atg gga tac cac aaa aaa acc tat gga
ggc tac 639 Asp Val Phe Val Ser Met Gly Tyr His Lys Lys Thr Tyr Gly
Gly Tyr 95 100 105 cag ggt aga gtg ttt ctg aag gga ggc agt gat agt
gat gct tct ctg 687 Gln Gly Arg Val Phe Leu Lys Gly Gly Ser Asp Ser
Asp Ala Ser Leu 110 115 120 gtc atc aca gac ctc act ctg gaa gat tat
ggg aga tat aag tgt gag 735 Val Ile Thr Asp Leu Thr Leu Glu Asp Tyr
Gly Arg Tyr Lys Cys Glu 125 130 135 140 gtg att gaa gga tta gaa gat
gat act gtt gtg gta gca ctg gac tta 783 Val Ile Glu Gly Leu Glu Asp
Asp Thr Val Val Val Ala Leu Asp Leu 145 150 155 caa ggt gtg gta ttc
cct tac ttt cca cga ctg ggg cgc tac aat ctc 831 Gln Gly Val Val Phe
Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu 160 165 170 aat ttt cac
gag gcg cag cag gcg tgt ctg gac cag gat gct gtg atc 879 Asn Phe His
Glu Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile 175 180 185 gcc
tcc ttc gac cag ctg tac gac gcc tgg cgg ggc ggg ctg gac tgg 927 Ala
Ser Phe Asp Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp 190 195
200 tgc aat gcc ggc tgg ctc agt gat ggc tct gtg caa tat ccc atc aca
975 Cys Asn Ala Gly Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr
205 210 215 220 aag ccc aga gag ccc tgt ggg ggc cag aac aca gtg ccc
gga gtc agg 1023 Lys Pro Arg Glu Pro Cys Gly Gly Gln Asn Thr Val
Pro Gly Val Arg 225 230 235 aac tac gga ttt tgg gat aaa gat aaa agc
aga tat gat gtt ttc tgt 1071 Asn Tyr Gly Phe Trp Asp Lys Asp Lys
Ser Arg Tyr Asp Val Phe Cys 240 245 250 ttt aca tcc aat ttc aat ggc
cgt ttt tac tat ctg atc cac ccc acc 1119 Phe Thr Ser Asn Phe Asn
Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr 255 260 265 aaa ctg acc tat
gat gaa gcg gtg caa gct tgt ctc aat gat ggt gct 1167 Lys Leu Thr
Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala 270 275 280 cag
att gca aaa gtg ggc cag ata ttt gct gcc tgg aaa att ctc gga 1215
Gln Ile Ala Lys Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly 285
290 295 300 tat gac cgc tgt gat gcg ggc tgg ttg gcg gat ggc agc gtc
cgc tac 1263 Tyr Asp Arg Cys Asp Ala Gly Trp Leu Ala Asp Gly Ser
Val Arg Tyr 305 310 315 ccc atc tct agg cca aga agg cgc tgc agt cct
act gag gct gca gtg 1311 Pro Ile Ser Arg Pro Arg Arg Arg Cys Ser
Pro Thr Glu Ala Ala Val 320 325 330 cgc ttc gtg ggt ttc cca gat aaa
aag cat aag ctg tat ggt gtc tac 1359 Arg Phe Val Gly Phe Pro Asp
Lys Lys His Lys Leu Tyr Gly Val Tyr 335 340 345 tgc ttc aga gca tac
aac tga atgtgccctt agagcgcatc agttttaaag 1410 Cys Phe Arg Ala Tyr
Asn * 350 tcattaagaa catgtgaaag gtgttttttt tttccaatat gaactcatgc
aagttaccaa 1470 aactgtgata accctttttt acttactgta aagagtcatt
ttcataagat caattcattg 1530 atttgttttt tgtaaagcta tcattcaata
tatattataa attaatataa atttaaggga 1590 agctctatgt aaggagactt
agagccaaac tgtttaagct gtatcatccc aacaaagtat 1650 cccttcatga
acggggcatg caatagctta agaattgcta ggattaaatt aaggaaagta 1710
aagctactca gagcaacagg ttccacaagc acaaacttta cacatttgta caattttgaa
1770 atgcactaca ataaacaaat tagagcaaca catttgaaat acaggcttct
ttacataaac 1830 tgagaggtta tacaaaactc agtttcacaa gggaacaatc
tatacctttc taaaagttaa 1890 tatttcaagt ctctaatagg cagaatattt
tactctttaa aatcctgcct ttctgaccaa 1950 aaaaaaa 1957 21 354 PRT Homo
sapiens 21 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile Cys Trp
Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg
Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu Val
Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn
Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe
Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu
Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90 95 Ser Met
Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110
Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115
120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu
Gly 130 135 140 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln
Gly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr
Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln
Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp
Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp
Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys
Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235
240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn
245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu
Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala
Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile
Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly
Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys
Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe Pro Asp
Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr
Asn 22 1957 DNA Homo sapiens CDS (316)...(1380) 22 ttaggctgta
attaggggat ttgggaggag aactttcctg gtgacgcttt gcttttcttc 60
tgctcttggt gagaaagtgc ctccttcttc ccaggatcag gacctctgcc atccagcgcc
120 acaaagagac attctgcaca cacactcaca cacacacaca cacacacact
ctcacactcg 180 cccagagaca aacttaaggt gaggagaaag agcgctacgt
tcacttgatc tccagcttcc 240 aacttaagca gaacttgaga gcatccgaac
tcctggattt caggacaagt gaagaagatt 300 ctttgggcta taaag atg aag agt
cta ctt ctt ctg gtg ctg att tca atc 351 Met Lys Ser Leu Leu Leu Leu
Val Leu Ile Ser Ile 1 5 10 tgc tgg gct gat cat ctt tca gac aac tat
act ctg gat cat gac aga 399 Cys Trp Ala Asp His Leu Ser Asp Asn Tyr
Thr Leu Asp His Asp Arg 15 20 25 gct att cac atc caa gca gaa aat
ggc ccc cat cta ctt gtg gaa gca 447 Ala Ile His Ile Gln Ala Glu Asn
Gly Pro His Leu Leu Val Glu Ala 30 35 40 gag caa gcc aag gtg ttt
tca cac aga ggt ggc aat gtt aca ctg cca 495 Glu Gln Ala Lys Val Phe
Ser His Arg Gly Gly Asn Val Thr Leu Pro 45 50 55 60 tgt aaa ttt tat
cga gac cct aca gca ttt ggc tca gga atc cat aaa 543 Cys Lys Phe Tyr
Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys 65 70 75 atc cga
att aag tgg acc aag cta act tcg gat tac ctc aag gaa gtg 591 Ile Arg
Ile Lys Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val 80 85 90
gat gtt ttt gtt tcc atg gga tac cac aaa aaa acc tat gga ggc tac 639
Asp Val Phe Val Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr 95
100 105 cag ggt aga gtg ttt ctg aag gga ggc agt gat agt gat gct tct
ctg 687 Gln Gly Arg Val Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser
Leu 110 115 120 gtc atc aca gac ctc act ctg gaa gat tat ggg aga tat
aag tgt gag 735 Val Ile Thr Asp Leu Thr Leu Glu Asp Tyr Gly Arg Tyr
Lys Cys Glu 125 130 135 140 gtg att gaa gga tta gaa gat gat act gtt
gtg gta gca ctg gac tta 783 Val Ile Glu Gly Leu Glu Asp Asp Thr Val
Val Val Ala Leu Asp Leu 145 150 155 caa ggt gtg gta ttc cct tac ttt
cca cga ctg ggg cgc tac aat ctc 831 Gln Gly Val Val Phe Pro Tyr Phe
Pro Arg Leu Gly Arg Tyr Asn Leu 160 165 170 aat ttt cac gag gcg cag
cag gcg tgt ctg gac cag gat gct gtg atc 879 Asn Phe His Glu Ala Gln
Gln Ala Cys Leu Asp Gln Asp Ala Val Ile 175 180 185 gcc tcc ttc gac
cag ctg tac gac gcc tgg cgg ggc ggg ctg gac tgg 927 Ala Ser Phe Asp
Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp 190 195 200 tgc aat
gcc ggc tgg ctc agt gat ggc tct gtg caa tat ccc atc aca 975 Cys Asn
Ala Gly Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr 205 210 215
220 aag ccc aga gag ccc tgt ggg ggc cag aac aca gtg ccc gga gtc agg
1023 Lys Pro Arg Glu Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val
Arg 225 230
235 aac tac gga ttt tgg gat aaa gat aaa agc aga tat gat gtt ttc tgt
1071 Asn Tyr Gly Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe
Cys 240 245 250 ttt aca tcc aat ttc aat ggc cgt ttt tac tat ctg atc
cac ccc acc 1119 Phe Thr Ser Asn Phe Asn Gly Arg Phe Tyr Tyr Leu
Ile His Pro Thr 255 260 265 aaa ctg acc tat gat gaa gcg gtg caa gct
tgt ctc aat gat ggt gct 1167 Lys Leu Thr Tyr Asp Glu Ala Val Gln
Ala Cys Leu Asn Asp Gly Ala 270 275 280 cag att gca aaa gtg ggc cag
ata ttt gct gcc tgg aaa att ctc gga 1215 Gln Ile Ala Lys Val Gly
Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly 285 290 295 300 tat gac cgc
tgt gat gcg ggc tgg ttg gcg gat ggc agc gtc cgc tac 1263 Tyr Asp
Arg Cys Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr 305 310 315
ccc atc tct agg cca aga agg cgc tgc agt cct act gag gct gca gtg
1311 Pro Ile Ser Arg Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala
Val 320 325 330 cgc ttc gtg ggt ttc cca gat aaa aag cat aag ctg tat
ggt gtc tac 1359 Arg Phe Val Gly Phe Pro Asp Lys Lys His Lys Leu
Tyr Gly Val Tyr 335 340 345 tgc ttc aga gca tac aac tga atgtgccctt
agagcgcatc agttttaaag 1410 Cys Phe Arg Ala Tyr Asn * 350 tcattaagaa
catgtgaaag gtgttttttt tttccaatat gaactcatgc aagttaccaa 1470
aactgtgata accctttttt acttactgta aagagtcatt ttcataagat caattcattg
1530 atttgttttt tgtaaagcta tcattcaata tatattataa attaatataa
atttaaggga 1590 agctctatgt aaggagactt agagccaaac tgtttaagct
gtatcatccc aacaaagtat 1650 cctttcatga acggggcatg caatagctta
agaattgcta ggattaaatt aaggaaagta 1710 aagctactca gagcagcagg
ttccacaagc acaaacttta cacatttgta caattttgaa 1770 atgcactaca
ataaacaaat tagagcaaca catttgaaat acaggcttct ttacataaac 1830
tgagaggtta tacaaaactc agtttcacaa gggaacaatc tatacctttc taaaagttaa
1890 tatttcaagt ctctaatagg cagaatattt tactctttaa aatcctgcct
ttctgaccaa 1950 aaaaaaa 1957 23 354 PRT Homo sapiens 23 Met Lys Ser
Leu Leu Leu Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His
Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 20 25
30 Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys
35 40 45 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys
Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys
Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys
Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr
Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser
Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu
Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu
Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155
160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu
165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser
Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp
Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro
Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val
Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys
Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly
Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp
Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275 280
285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys
290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile
Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala
Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr
Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 24 354 PRT Homo
sapiens 24 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile Cys Trp
Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg
Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu Val
Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn
Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe
Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu
Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90 95 Ser Met
Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110
Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115
120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu
Gly 130 135 140 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln
Gly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr
Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln
Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp
Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp
Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys
Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235
240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn
245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu
Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala
Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile
Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly
Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys
Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe Pro Asp
Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr
Asn 25 721 PRT Homo sapiens 25 Met Leu Glu His Thr Thr Lys Thr Phe
Pro Leu Arg Ala Leu His Ile 1 5 10 15 Val Val Glu Ser Ile Arg Asp
His Ser Gly Gln Lys Met Lys Gln Asp 20 25 30 Lys Lys Val Asp Leu
Leu Val Pro Thr Lys Val Thr Gly Ile Ile Thr 35 40 45 Gln Gly Ala
Lys Asp Phe Gly His Val Gln Phe Val Gly Ser Tyr Lys 50 55 60 Leu
Ala Tyr Ser Asn Asp Gly Glu His Trp Thr Val Tyr Gln Asp Glu 65 70
75 80 Lys Gln Arg Lys Asp Lys Val Leu Leu Gly Arg Lys Ala Val Val
Val 85 90 95 Ser Cys Glu Gly Ile Asn Ile Ser Gly Ser Phe Cys Arg
Asn Lys Leu 100 105 110 Lys Tyr Leu Ala Phe Leu His Lys Arg Met Asn
Thr Asn Pro Ser Arg 115 120 125 Arg Pro Tyr His Phe Gln Val Pro Ser
Arg Ile Phe Trp Arg Gln Glu 130 135 140 Lys Ala Asp Gly Gly Ser Cys
Cys Pro Gln Gly His Ala Ser Glu Ala 145 150 155 160 Tyr Lys Lys Val
Cys Leu Ser Gly Ala Pro His Glu Val Gly Trp Lys 165 170 175 Tyr Gln
Ala Val Thr Ala Thr Leu Glu Glu Lys Arg Lys Glu Lys Ala 180 185 190
Glu Ile His Tyr Arg Lys Asn Lys Gln Leu Met Arg Leu Gln Lys Gln 195
200 205 Ala Glu Lys Asn Met Lys Lys Lys Ile Asp Lys Tyr Thr Glu Ser
Pro 210 215 220 Gly Gly Gly Ser Pro Arg Gly Leu Gly Phe Ile Phe Lys
Thr Ile Ala 225 230 235 240 Pro Leu Ala Ala Thr Arg Ala Thr Arg Ile
Gly His Pro Gly Gly Arg 245 250 255 Thr Pro Arg Ala Gly Ser Ser Ala
His Arg Pro Pro Ala Leu Ser Ala 260 265 270 Arg Ala Pro Val Pro Ala
Ala Ser Pro Ala Ala Trp Leu Pro Leu Arg 275 280 285 Thr Pro Trp Thr
Arg Pro Ser Ser Cys Pro Thr Ser Ser Ser Thr Tyr 290 295 300 Asp Ser
Leu Ser Pro Tyr Gly Pro Arg Asn Pro Leu Pro Asn Pro Arg 305 310 315
320 His Ser Pro Ser Gly Gly Gly Gly Leu Lys Lys Pro Ala Arg His Cys
325 330 335 Gln Gly Gln Lys His Asn Val Leu Ala Arg Gly Lys Pro Gln
Arg Lys 340 345 350 Pro Lys Ser Glu Asn Asn Ser Trp Tyr Val Glu Asn
Gly Arg Pro Ala 355 360 365 Asp Leu Ala Gly Ser Gly Tyr Cys Gly Ala
Leu Trp Lys Ala Ile Glu 370 375 380 Ser Leu Glu Glu Gly Leu Gly Gly
Lys Gln Lys Asp Lys Glu Arg Lys 385 390 395 400 Ala Glu Asn Gly Pro
His Leu Leu Val Glu Ala Glu Gln Ala Lys Val 405 410 415 Phe Ser His
Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr Arg 420 425 430 Asp
Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys Trp 435 440
445 Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val Ser
450 455 460 Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg
Val Phe 465 470 475 480 Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu
Val Ile Thr Asp Leu 485 490 495 Thr Leu Glu Asp Tyr Gly Arg Tyr Lys
Cys Glu Val Ile Glu Gly Leu 500 505 510 Glu Asp Asp Thr Val Val Val
Ala Leu Asp Leu Gln Gly Val Val Phe 515 520 525 Pro Tyr Phe Pro Arg
Leu Gly Arg Tyr Asn Leu Asn Phe His Glu Ala 530 535 540 Gln Gln Ala
Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp Gln 545 550 555 560
Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly Trp 565
570 575 Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu
Pro 580 585 590 Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr
Gly Phe Trp 595 600 605 Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys
Phe Thr Ser Asn Phe 610 615 620 Asn Gly Arg Phe Tyr Tyr Leu Ile His
Pro Thr Lys Leu Thr Tyr Asp 625 630 635 640 Glu Ala Val Gln Ala Cys
Leu Asn Asp Gly Ala Gln Ile Ala Lys Val 645 650 655 Gly Gln Ile Phe
Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys Asp 660 665 670 Ala Gly
Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg Pro 675 680 685
Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly Phe 690
695 700 Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala
Tyr 705 710 715 720 Asn 26 1957 DNA Homo sapiens 26 ttaggctgta
attaggggat ttgggaggag aactttcctg gtgacgcttt gcttttcttc 60
tgctcttggt gagaaagtgc ctccttcttc ccaggatcag gacctctgcc atccagcgcc
120 acaaagagac attctgcaca cacactcaca cacacacaca cacacacact
ctcacactcg 180 cccagagaca aacttaaggt gaggagaaag agcgctacgt
tcacttgatc tccagcttcc 240 aacttaagca gaacttgaga gcatccgaac
tcctggattt caggacaagt gaagaagatt 300 ctttgggcta taaagatgaa
gagtctactt cttctggtgc tgatttcaat ctgctgggct 360 gatcatcttt
cagacaacta tactctggat catgacagag ctattcacat ccaagcagaa 420
aatggccccc atctacttgt ggaagcagag caagccaagg tgttttcaca cagaggtggc
480 aatgttacac tgccatgtaa attttatcga gaccctacag catttggctc
aggaatccat 540 aaaatccgaa ttaagtggac caagctaact tcggattacc
tcaaggaagt ggatgttttt 600 gtttccatgg gataccacaa aaaaacctat
ggaggctacc agggtagagt gtttctgaag 660 ggaggcagtg atagtgatgc
ttctctggtc atcacagacc tcactctgga agattatggg 720 agatataagt
gtgaggtgat tgaaggatta gaagatgata ctgttgtggt agcactggac 780
ttacaaggtg tggtattccc ttactttcca cgactggggc gctacaatct caattttcac
840 gaggcgcagc aggcgtgtct ggaccaggat gctgtgatcg cctccttcga
ccagctgtac 900 gacgcctggc ggggcgggct ggactggtgc aatgccggct
ggctcagtga tggctctgtg 960 caatatccca tcacaaagcc cagagagccc
tgtgggggcc agaacacagt gcccggagtc 1020 aggaactacg gattttggga
taaagataaa agcagatatg atgttttctg ttttacatcc 1080 aatttcaatg
gccgttttta ctatctgatc caccccacca aactgaccta tgatgaagcg 1140
gtgcaagctt gtctcaatga tggtgctcag attgcaaaag tgggccagat atttgctgcc
1200 tggaaaattc tcggatatga ccgctgtgat gcgggctggt tggcggatgg
cagcgtccgc 1260 taccccatct ctaggccaag aaggcgctgc agtcctactg
aggctgcagt gcgcttcgtg 1320 ggtttcccag ataaaaagca taagctgtat
ggtgtctact gcttcagagc atacaactga 1380 atgtgccctt agagcgcatc
agttttaaag tcattaagaa catgtgaaag gtgttttttt 1440 tttccaatat
gaactcatgc aagttaccaa aactgtgata accctttttt acttactgta 1500
aagagtcatt ttcataagat caattcattg atttgttttt tgtaaagcta tcattcaata
1560 tatattataa attaatataa atttaaggga agctctatgt aaggagactt
agagccaaac 1620 tgtttaagct gtatcatccc aacaaagtat cctttcatga
acggggcatg caatagctta 1680 agaattgcta ggattaaatt aaggaaagta
aagctactca gagcaacagg ttccacaagc 1740 acaaacttta cacatttgta
caattttgaa atgcactaca ataaacaaat tagagcaaca 1800 catttgaaat
acaggcttct ttacataaac tgagaggtta tacaaaactc agtttcacaa 1860
gggaacaatc tatacctttc taaaagttaa tatttcaagt ctctaatagg cagaatattt
1920 tactctttaa aatcctgcct ttctgaccaa aaaaaaa 1957 27 1492 DNA Homo
sapiens 27 ttaggctgta attaggggat ttgggaggag aactttcctg gtgacgcttt
gcttttcttc 60 tgctcttggt gagaaagtgc ctccttcttc ccaggatcag
gacctctgcc atccagcgcc 120 acaaagagac attctgcaca cacactcaca
cacacacaca cacacacact ctcacactcg 180 cccagagaca aacttaaggt
gaggagaaag agcgctagct tcacttgatc tccagcttcc 240 aacttaagca
gaacttgaga gcatccgaac tcctggattt caggacaagt gaagaagatt 300
ctttgggcta taaagatgaa gagtctactt cttctggtgc tgatttcaat ctgctgggct
360 gatcatcttt cagacaacta tactctggat catgacagag ctattcacat
ccaagcagaa 420 aatggccccc atctacttgt ggaagcagag caagccaagg
tgttttcaca cagaggtggc 480 aatgttacac tgccatgtaa attttatcga
gaccctacag catttggctc aggaatccat 540 aaaatccgaa ttaagtggac
caagctaact tcggattacc tcaaggaagt ggatgttttt 600 gtttccatgg
gataccacaa aaaaacctat ggaggctacc agggtagagt gtttctgaag 660
ggaggcagtg atagtgatgc ttctctggtc atcacagacc tcactctgga agattatggg
720 agatataagt gtgaggtgat tgaaggatta gaagatgata ctgttgtggt
agcactggac 780 ttacaaggtg tggtattccc ttactttcca cgactggggc
gctacaatct caattttcac 840 gaggcgcagc aggcgtgtct ggaccaggat
gctgtgatcg cctccttcga ccagctgtac 900 gacgcctggc ggggcgggct
ggactggtgc aatgccggct ggctcagtga tggctctgtg 960 caatatccca
tcacaaagcc cagagagccc tgtgggggcc agaacacagt gcccggagtc 1020
aggaactacg gattttggga taaagataaa agcagatatg atgttttctg ttttacatcc
1080 aatttcaatg gccgttttta ctatctgatc caccccacca aactgaccta
tgatgaagcg 1140 gtgcaagctt gtctcaatga tggtgctcag attgcaaaag
tgggccagat atttgctgcc 1200 tggaaaattc tcggatatga ccgctgtgat
gcgggctggt tggcggatgg cagcgtccgc 1260 taccccatct ctaggccaag
aaggcgctgc agtcctactg aggctgcagt gcgcttcgtg 1320 ggttttccag
ataaaaagca taagctgtat ggtgtctact gcttcagagc atacaactga 1380
atgtgccctt agagcgcact agttttaaag tcattaagaa catgtgaaag gtgttttttt
1440 tttccaatat gaactcatgc aagttaccaa aactgtgata accctttttt ac 1492
28 354 PRT Homo sapiens 28 Met Lys Ser Leu Leu Leu Leu Val Leu Ile
Ser Ile Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu
Asp His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro
His Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His
Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp
Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80
Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85
90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg
Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val
Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys
Glu Val Ile Glu Gly 130
135 140 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val
Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu
Asn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala
Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly
Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser
Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys Gly Gly
Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235 240 Trp
Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250
255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr
260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile
Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly
Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val
Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro
Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys
His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 29
354 PRT Homo sapiens 29 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser
Ile Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp
His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His
Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg
Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro
Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp
Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90
95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val
100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile
Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu
Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr Val Val Val Ala Leu
Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg Leu
Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys
Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr
Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp
Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215
220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe
225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe
Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro
Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn
Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala
Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu
Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg
Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335
Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340
345 350 Tyr Asn 30 354 PRT Homo sapiens 30 Met Lys Ser Leu Leu Leu
Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp
Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala
Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45
Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50
55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile
Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp
Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly
Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp
Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly
Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr
Val Val Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro
Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175
Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180
185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala
Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys
Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val
Arg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr
Asp Val Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr
Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val
Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly
Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300
Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305
310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe
Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr
Cys Phe Arg Ala 340 345 350 Tyr Asn 31 355 PRT Mus musculus 31 Met
Arg Ser Leu Leu Leu Leu Val Leu Ile Ser Val Cys Trp Ala Asp 1 5 10
15 His Leu Ser Asp Ser Tyr Thr Pro Pro Asp Gln Asp Arg Val Ile His
20 25 30 Ile Gln Ala Glu Asn Gly Pro Arg Leu Leu Val Glu Ala Glu
Gln Ala 35 40 45 Lys Val Phe Ser His Arg Gly Gly Asn Val Thr Leu
Pro Cys Lys Phe 50 55 60 Tyr Arg Asp Pro Thr Ala Phe Gly Ser Gly
Ile His Lys Ile Arg Ile 65 70 75 80 Lys Trp Thr Lys Leu Thr Ser Asp
Tyr Leu Arg Glu Val Asp Val Phe 85 90 95 Val Ser Met Gly Tyr His
Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg 100 105 110 Val Phe Leu Lys
Gly Gly Ser Asp Asn Asp Ala Ser Leu Val Ile Thr 115 120 125 Asp Leu
Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu 130 135 140
Gly Leu Glu Asp Asp Thr Ala Val Val Ala Leu Glu Leu Gln Gly Val 145
150 155 160 Val Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn
Phe His 165 170 175 Glu Ala Arg Gln Ala Cys Leu Asp Gln Asp Ala Val
Ile Ala Ser Phe 180 185 190 Asp Gln Leu Tyr Asp Ala Trp Arg Gly Gly
Leu Asp Trp Cys Asn Ala 195 200 205 Gly Trp Leu Ser Asp Gly Ser Val
Gln Tyr Pro Ile Thr Lys Pro Arg 210 215 220 Glu Pro Cys Gly Gly Gln
Asn Thr Val Pro Gly Val Arg Asn Tyr Gly 225 230 235 240 Phe Trp Asp
Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser 245 250 255 Asn
Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr 260 265
270 Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala
275 280 285 Lys Val Gly Gln Ile Phe Ala Ala Trp Lys Leu Leu Gly Tyr
Asp Arg 290 295 300 Cys Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg
Tyr Pro Ile Ser 305 310 315 320 Arg Pro Arg Arg Arg Cys Ser Pro Thr
Glu Ala Ala Val Arg Phe Val 325 330 335 Gly Phe Pro Asp Lys Lys His
Lys Leu Tyr Gly Val Tyr Cys Phe Arg 340 345 350 Ala Tyr Asn 355 32
322 PRT Homo sapiens 32 Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu
Ala Glu Gln Ala Lys 1 5 10 15 Val Phe Ser His Arg Gly Gly Asn Val
Thr Leu Pro Cys Lys Phe Tyr 20 25 30 Arg Asp Pro Thr Ala Phe Gly
Ser Gly Ile His Lys Ile Arg Ile Lys 35 40 45 Trp Thr Lys Leu Thr
Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 50 55 60 Ser Met Gly
Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 65 70 75 80 Phe
Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 85 90
95 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly
100 105 110 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly
Val Val 115 120 125 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu
Asn Phe His Glu 130 135 140 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala
Val Ile Ala Ser Phe Asp 145 150 155 160 Gln Leu Tyr Asp Ala Trp Arg
Gly Gly Leu Asp Trp Cys Asn Ala Gly 165 170 175 Trp Leu Ser Asp Gly
Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 180 185 190 Pro Cys Gly
Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 195 200 205 Trp
Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 210 215
220 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr
225 230 235 240 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln
Ile Ala Lys 245 250 255 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu
Gly Tyr Asp Arg Cys 260 265 270 Asp Ala Gly Trp Leu Ala Asp Gly Ser
Val Arg Tyr Pro Ile Ser Arg 275 280 285 Pro Arg Arg Arg Cys Ser Pro
Thr Glu Ala Ala Val Arg Phe Val Gly 290 295 300 Phe Pro Asp Lys Lys
His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 305 310 315 320 Tyr Asn
33 322 PRT Homo sapiens 33 Lys Ala Glu Asn Gly Pro His Leu Leu Val
Glu Ala Glu Gln Ala Lys 1 5 10 15 Val Phe Ser His Arg Gly Gly Asn
Val Thr Leu Pro Cys Lys Phe Tyr 20 25 30 Arg Asp Pro Thr Ala Phe
Gly Ser Gly Ile His Lys Ile Arg Ile Lys 35 40 45 Trp Thr Lys Leu
Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 50 55 60 Ser Met
Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 65 70 75 80
Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 85
90 95 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu
Gly 100 105 110 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln
Gly Val Val 115 120 125 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn
Leu Asn Phe His Glu 130 135 140 Ala Gln Gln Ala Cys Leu Asp Gln Asp
Ala Val Ile Ala Ser Phe Asp 145 150 155 160 Gln Leu Tyr Asp Ala Trp
Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 165 170 175 Trp Leu Ser Asp
Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 180 185 190 Pro Cys
Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 195 200 205
Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 210
215 220 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr
Tyr 225 230 235 240 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala
Gln Ile Ala Lys 245 250 255 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile
Leu Gly Tyr Asp Arg Cys 260 265 270 Asp Ala Gly Trp Leu Ala Asp Gly
Ser Val Arg Tyr Pro Ile Ser Arg 275 280 285 Pro Arg Arg Arg Cys Ser
Pro Thr Glu Ala Ala Val Arg Phe Val Gly 290 295 300 Phe Pro Asp Lys
Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 305 310 315 320 Tyr
Asn 34 168 PRT Homo sapiens 34 Met Asn Thr Asn Pro Ser Arg Arg Pro
Tyr His Phe Gln Val Pro Ser 1 5 10 15 Arg Ile Phe Trp Arg Gln Glu
Lys Ala Asp Gly Gly Ser Cys Cys Pro 20 25 30 Gln Gly His Ala Ser
Glu Ala Tyr Lys Lys Val Cys Leu Ser Gly Ala 35 40 45 Pro His Glu
Val Gly Trp Lys Tyr Gln Ala Val Thr Ala Thr Leu Glu 50 55 60 Glu
Lys Arg Lys Glu Lys Ala Glu Ile His Tyr Arg Lys Asn Lys Gln 65 70
75 80 Leu Met Arg Leu Gln Lys Gln Ala Glu Lys Asn Met Lys Lys Lys
Ile 85 90 95 Asp Lys Tyr Thr Glu Ser Pro Gly Gly Gly Ser Pro Arg
Gly Leu Gly 100 105 110 Phe Ile Phe Lys Thr Ile Ala Pro Leu Ala Ala
Thr Arg Ala Thr Arg 115 120 125 Ile Gly His Pro Gly Gly Arg Thr Pro
Arg Ala Gly Ser Ser Ala His 130 135 140 Arg Pro Pro Ala Leu Ser Ala
Arg Ala Pro Val Pro Ala Ala Ser Pro 145 150 155 160 Ala Ala Trp Leu
Pro Leu Arg Thr 165 35 168 PRT Homo sapiens 35 Met Asn Thr Asn Pro
Ser Arg Arg Pro Tyr His Phe Gln Val Pro Ser 1 5 10 15 Arg Ile Phe
Trp Arg Gln Glu Lys Ala Asp Gly Gly Ser Cys Cys Pro 20 25 30 Gln
Gly His Ala Ser Glu Ala Tyr Lys Lys Val Cys Leu Ser Gly Ala 35 40
45 Pro His Glu Val Gly Trp Lys Tyr Gln Ala Val Thr Ala Thr Leu Glu
50 55 60 Glu Lys Arg Lys Glu Lys Ala Glu Ile His Tyr Arg Lys Asn
Lys Gln 65 70 75 80 Leu Met Arg Leu Gln Lys Gln Ala Glu Lys Asn Met
Lys Lys Lys Ile 85 90 95 Asp Lys Tyr Thr Glu Ser Pro Gly Gly Gly
Ser Pro Arg Gly Leu Gly 100 105 110 Phe Ile Phe Lys Thr Ile Ala Pro
Leu Ala Ala Thr Arg Ala Thr Arg 115 120 125 Ile Gly His Pro Gly Gly
Arg Thr Pro Arg Ala Gly Ser Ser Ala His 130 135 140 Arg Pro Pro Ala
Leu Ser Ala Arg Ala Pro Val Pro Ala Ala Ser Pro 145 150 155 160 Ala
Ala Trp Leu Pro Leu Arg Ser 165 36 354 PRT Homo sapiens 36 Met Lys
Ser Leu Leu Leu Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15
His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 20
25 30 Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala
Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys
Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His
Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu
Lys Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys
Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly
Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu
Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu
Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val 145 150
155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His
Glu
165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser
Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp
Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro
Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val
Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys
Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly
Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp
Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275 280
285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys
290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile
Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala
Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr
Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 37 354 PRT Homo
sapiens 37 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Phe Cys Trp
Ala Asp 1 5 10 15 His His Ser Asp Asn Tyr Thr Val Asp His Asp Arg
Val Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro Arg Leu Leu Val
Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser Arg Arg Gly Gly Asn
Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe
Gly Ser Gly Thr His Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu
Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90 95 Ser Met
Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr His Gly Arg Val 100 105 110
Phe Leu Lys Gly Gly Ser Asp Asn Asp Ala Ser Leu Val Ile Thr Asp 115
120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu
Gly 130 135 140 Leu Glu Asp Asp Thr Ala Val Val Ala Leu Asp Leu Gln
Gly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr
Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln
Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp
Arg Ser Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp
Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys
Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235
240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn
245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu
Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala
Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Leu
Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly
Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys
Ser Pro Ser Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe Pro Asp
Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr
Asn 38 354 PRT Homo sapiens 38 Met Lys Ser Leu Leu Leu Leu Val Leu
Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr
Leu Asp His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly
Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser
His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg
Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70
75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe
Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln
Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser
Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr
Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr Val Val
Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr Phe
Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln
Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190
Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195
200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg
Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn
Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val
Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu
Ile His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala
Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile
Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala
Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315
320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly
325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe
Arg Ala 340 345 350 Tyr Asn 39 354 PRT Rattus norvegicus 39 Met Arg
Ser Leu Leu Phe Leu Val Leu Ile Ser Val Cys Arg Ala Asp 1 5 10 15
His Leu Ser Asp Ser Tyr Thr Pro Asp Gln Asp Arg Val Ile His Ile 20
25 30 Gln Ala Glu Asn Gly Pro Arg Leu Leu Val Glu Ala Glu Gln Ala
Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys
Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His
Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu
Arg Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys
Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly
Ser Asp Asn Asp Ala Ser Leu Ile Ile Thr Asp 115 120 125 Leu Thr Leu
Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu
Glu Asp Asp Thr Ala Val Val Ala Leu Glu Leu Gln Gly Val Val 145 150
155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His
Glu 165 170 175 Ala Arg Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala
Ser Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp
Trp Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr
Pro Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr
Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp
Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn
Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260 265 270
Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275
280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Leu Leu Gly Tyr Asp Arg
Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro
Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala
Ala Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu
Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 40 201 PRT Homo
sapiens 40 Lys Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln
Ala Lys 1 5 10 15 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro
Cys Lys Phe Tyr 20 25 30 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile
His Lys Ile Arg Ile Lys 35 40 45 Trp Thr Lys Leu Thr Ser Asp Tyr
Leu Lys Glu Val Asp Val Phe Val 50 55 60 Ser Met Gly Tyr His Lys
Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 65 70 75 80 Phe Leu Lys Gly
Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 85 90 95 Leu Thr
Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 100 105 110
Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val 115
120 125 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His
Glu 130 135 140 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala
Ser Phe Asp 145 150 155 160 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu
Asp Trp Cys Asn Ala Gly 165 170 175 Trp Leu Ser Asp Gly Ser Val Gln
Tyr Pro Ile Thr Lys Pro Arg Glu 180 185 190 Pro Cys Gly Gly Gln Asn
Thr Val Pro 195 200 41 201 PRT Homo sapiens 41 Gln Ala Glu Asn Gly
Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 1 5 10 15 Val Phe Ser
His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 20 25 30 Arg
Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 35 40
45 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val
50 55 60 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly
Arg Val 65 70 75 80 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu
Val Ile Thr Asp 85 90 95 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys
Cys Glu Val Ile Glu Gly 100 105 110 Leu Glu Asp Asp Thr Val Val Val
Ala Leu Asp Leu Gln Gly Val Val 115 120 125 Phe Pro Tyr Phe Pro Arg
Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 130 135 140 Ala Gln Gln Ala
Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 145 150 155 160 Gln
Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 165 170
175 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu
180 185 190 Pro Cys Gly Gly Gln Asn Thr Val Pro 195 200 42 354 PRT
Homo sapiens 42 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile Cys
Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp
Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu
Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly
Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala
Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys
Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90 95 Ser
Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105
110 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp
115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile
Glu Gly 130 135 140 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu
Gln Gly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg
Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys Leu Asp
Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr Asp Ala
Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp Leu Ser
Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 Pro
Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230
235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser
Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys
Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly
Ala Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys
Ile Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp
Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg
Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe Pro
Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350
Tyr Asn 43 721 PRT Homo sapiens 43 Met Leu Glu His Thr Thr Lys Thr
Phe Pro Leu Arg Ala Leu His Ile 1 5 10 15 Val Val Glu Ser Ile Arg
Asp His Ser Gly Gln Lys Met Lys Gln Asp 20 25 30 Lys Lys Val Asp
Leu Leu Val Pro Thr Lys Val Thr Gly Ile Ile Thr 35 40 45 Gln Gly
Ala Lys Asp Phe Gly His Val Gln Phe Val Gly Ser Tyr Lys 50 55 60
Leu Ala Tyr Ser Asn Asp Gly Glu His Trp Thr Val Tyr Gln Asp Glu 65
70 75 80 Lys Gln Arg Lys Asp Lys Val Leu Leu Gly Arg Lys Ala Val
Val Val 85 90 95 Ser Cys Glu Gly Ile Asn Ile Ser Gly Ser Phe Cys
Arg Asn Lys Leu 100 105 110 Lys Tyr Leu Ala Phe Leu His Lys Arg Met
Asn Thr Asn Pro Ser Arg 115 120 125 Arg Pro Tyr His Phe Gln Val Pro
Ser Arg Ile Phe Trp Arg Gln Glu 130 135 140 Lys Ala Asp Gly Gly Ser
Cys Cys Pro Gln Gly His Ala Ser Glu Ala 145 150 155 160 Tyr Lys Lys
Val Cys Leu Ser Gly Ala Pro His Glu Val Gly Trp Lys 165 170 175 Tyr
Gln Ala Val Thr Ala Thr Leu Glu Glu Lys Arg Lys Glu Lys Ala 180 185
190 Glu Ile His Tyr Arg Lys Asn Lys Gln Leu Met Arg Leu Gln Lys Gln
195 200 205 Ala Glu Lys Asn Met Lys Lys Lys Ile Asp Lys Tyr Thr Glu
Ser Pro 210 215 220 Gly Gly Gly Ser Pro Arg Gly Leu Gly Phe Ile Phe
Lys Thr Ile Ala 225 230 235 240 Pro Leu Ala Ala Thr Arg Ala Thr Arg
Ile Gly His Pro Gly Gly Arg 245 250 255 Thr Pro Arg Ala Gly Ser Ser
Ala His Arg Pro Pro Ala Leu Ser Ala 260 265 270 Arg Ala Pro Val Pro
Ala Ala Ser Pro Ala Ala Trp Leu Pro Leu Arg 275 280 285 Thr Pro Trp
Thr Arg Pro Ser Ser Cys Pro Thr Ser Ser Ser Thr Tyr 290 295 300 Asp
Ser Leu Ser Pro Tyr Gly Pro Arg Asn Pro Leu Pro Asn Pro Arg 305 310
315 320 His Ser Pro Ser Gly Gly Gly Gly Leu Lys Lys Pro Ala Arg His
Cys 325 330 335 Gln Gly Gln Lys His Asn Val Leu Ala Arg Gly Lys Pro
Gln Arg Lys 340 345 350 Pro Lys Ser Glu Asn Asn Ser Trp Tyr Val Glu
Asn Gly Arg Pro Ala 355 360 365 Asp Leu Ala Gly Ser Gly Tyr Cys Gly
Ala Leu Trp Lys Ala Ile Glu 370 375 380 Ser Leu Glu Glu Gly Leu Gly
Gly Lys Gln Lys Asp Lys Glu Arg Lys 385 390 395 400 Ala Glu Asn Gly
Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys Val 405 410 415 Phe Ser
His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr Arg
420 425 430 Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile
Lys Trp 435 440 445 Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp
Val Phe Val Ser 450 455 460 Met Gly Tyr His Lys Lys Thr Tyr Gly Gly
Tyr Gln Gly Arg Val Phe 465 470 475 480 Leu Lys Gly Gly Ser Asp Ser
Asp Ala Ser Leu Val Ile Thr Asp Leu 485 490 495 Thr Leu Glu Asp Tyr
Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly Leu 500 505 510 Glu Asp Asp
Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val Phe 515 520 525 Pro
Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu Ala 530 535
540 Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp Gln
545 550 555 560 Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn
Ala Gly Trp 565 570 575 Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr
Lys Pro Arg Glu Pro 580 585 590 Cys Gly Gly Gln Asn Thr Val Pro Gly
Val Arg Asn Tyr Gly Phe Trp 595 600 605 Asp Lys Asp Lys Ser Arg Tyr
Asp Val Phe Cys Phe Thr Ser Asn Phe 610 615 620 Asn Gly Arg Phe Tyr
Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr Asp 625 630 635 640 Glu Ala
Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys Val 645 650 655
Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys Asp 660
665 670 Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg
Pro 675 680 685 Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe
Val Gly Phe 690 695 700 Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr
Cys Phe Arg Ala Tyr 705 710 715 720 Asn 44 14 PRT Tetanus Toxoid 44
Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly Ile Thr Glu 1 5 10 45
21 PRT Plasmodium falciparum 45 Asp Ile Glu Lys Lys Ile Ala Lys Met
Glu Lys Ala Ser Ser Val Phe 1 5 10 15 Asn Val Val Asn Ser 20 46 16
PRT Streptococcus 46 Gly Ala Val Asp Ser Ile Leu Gly Gly Val Ala
Thr Tyr Gly Ala Ala 1 5 10 15 47 13 PRT Artificial Sequence VARIANT
1, 13 Xaa = D-alanine 47 Xaa Lys Xaa Val Ala Ala Trp Thr Leu Lys
Ala Ala Xaa 1 5 10 48 14 DNA Artificial Sequence Primer 48
ttttgatcaa gctt 14 49 42 DNA Artificial Sequence Primer 49
ctaatacgac tcactatagg gctcgagcgg ccgcccgggc ag 42 50 12 DNA
Artificial Sequence Primer 50 gatcctgccc gg 12 51 40 DNA Artificial
Sequence Primer 51 gtaatacgac tcactatagg gcagcgtggt cgcggccgag 40
52 10 DNA Artificial Sequence Primer 52 gatcctcggc 10 53 22 DNA
Artificial Sequence PCR Primer 53 ctaatacgac tcactatagg gc 22 54 22
DNA Artificial Sequence Nested Primer 54 tcgagcggcc gcccgggcag ga
22 55 20 DNA Artificial Sequence Nested Primer 55 agcgtggtcg
cggccgagga 20 56 25 DNA Artificial Sequence Primer 56 atatcgccgc
gctcgtcgtc gacaa 25 57 26 DNA Artificial Sequence Primer 57
agccacacgc agctcattgt agaagg 26 58 24 DNA Artificial Sequence
RT-PCR Primer 58 cccaccaaac tgacctatga tgaa 24 59 25 DNA Artificial
Sequence RT-PCR Primer 59 tgtatgctct gaagcagtag acacc 25 60 24 DNA
Artificial Sequence Primer 60 gattacaagg atgacgacga taag 24 61 2166
DNA Homo sapiens 61 atgttggagc atactactaa gacattcccc ttaagagcac
tgcacatagt tgtggaaagc 60 attagggacc acagtggcca aaaaatgaag
caggataaga aggtggatct tcttgttcca 120 accaaagtga ctggcatcat
tacacaagga gctaaagatt ttggtcatgt acagtttgtt 180 ggctcctaca
aactggctta cagcaatgat ggagaacact ggactgtata ccaggatgaa 240
aagcaaagaa aagataaggt actgctgggc cggaaggcgg tggtcgtaag ctgcgaaggc
300 atcaacattt ctggcagttt ctgcagaaac aagttgaagt acctggcttt
cctccacaag 360 cggatgaaca ccaacccttc tcgacgcccc taccacttcc
aggtccccag ccgcatcttc 420 tggcgacaag aaaaagcaga tggtggttcc
tgctgccctc aaggtcatgc gtctgaagcc 480 tacaagaaag tttgcctatc
tggggcgcct cacgaggttg gctggaagta ccaggcagtg 540 acagccaccc
tggaggaaaa gaggaaagag aaagccgaga tccactaccg gaagaataaa 600
cagctcatga ggctacagaa acaggccgag aagaacatga agaagaaaat tgacaaatac
660 acagagagtc caggaggagg cagtccccgt ggcttaggct ttatctttaa
gacaatagcg 720 ccgctcgccg ccacccgcgc gactcggatc gggcatcccg
gcggccgcac cccgcgcgct 780 ggctcatctg cacaccggcc acctgcattg
tcggccagag cccccgtccc ggcggcttcc 840 ccagcagctt ggctgcccct
caggacgccc tggacccgcc catcctcctg ccccactagc 900 tcatcgactt
acgactccct cagtccctac ggcccacgga accctctccc caacccgcgc 960
cacagcccga gcggcggcgg cggccttaag aagcccgcaa gacactgtca aggtcaaaag
1020 cacaatgtgc tagccagggg gaaaccccag agaaagccaa aatctgaaaa
taacagctgg 1080 tatgtagaaa acggcagacc tgctgacttg gcaggctcag
gatattgtgg tgctctttgg 1140 aaggcaatag agtccttgga ggaaggactt
ggaggaaaac aaaaggacaa ggaaaggaaa 1200 gcagaaaatg gcccccatct
acttgtggaa gcagagcaag ccaaggtgtt ttcacacaga 1260 ggtggcaatg
ttacactgcc atgtaaattt tatcgagacc ctacagcatt tggctcagga 1320
atccataaaa tccgaattaa gtggaccaag ctaacttcgg attacctcaa ggaagtggat
1380 gtttttgttt ccatgggata ccacaaaaaa acctatggag gctaccaggg
tagagtgttt 1440 ctgaagggag gcagtgatag tgatgcttct ctggtcatca
cagacctcac tctggaagat 1500 tatgggagat ataagtgtga ggtgattgaa
ggattagaag atgatactgt tgtggtagca 1560 ctggacttac aaggtgtggt
attcccttac tttccacgac tggggcgcta caatctcaat 1620 tttcacgagg
cgcagcaggc gtgtctggac caggatgctg tgatcgcctc cttcgaccag 1680
ctgtacgacg cctggcgggg cgggctggac tggtgcaatg ccggctggct cagtgatggc
1740 tctgtgcaat atcccatcac aaagcccaga gagccctgtg gggggcagaa
cacagtgccc 1800 ggagtcagga actacggatt ttgggataaa gataaaagca
gatatgatgt tttctgtttt 1860 acatccaatt tcaatggccg tttttactat
ctgatccacc ccaccaaact gacctatgat 1920 gaagcggtgc aagcttgtct
caatgatggt gctcagattg caaaagtggg ccagatattt 1980 gctgcctgga
aaattctcgg atatgaccgc tgtgatgcgg gctggttggc ggatggcagc 2040
gtccgctacc ccatctctag gccaagaagg cgctgcagtc ctactgaggc tgcagtgcgc
2100 ttcgtgggtt tcccagataa aaagcataag ctgtatggtg tctactgctt
cagagcatac 2160 aactga 2166 62 1957 DNA Homo sapiens 62 ttaggctgta
attaggggat ttgggaggag aactttcctg gtgacgcttt gcttttcttc 60
tgctcttggt gagaaagtgc ctccttcttc ccaggatcag gacctctgcc atccagcgcc
120 acaaagagac attctgcaca cacactcaca cacacacaca cacacacact
ctcacactcg 180 cccagagaca aacttaaggt gaggagaaag agcgctacgt
tcacttgatc tccagcttcc 240 aacttaagca gaacttgaga gcatccgaac
tcctggattt caggacaagt gaagaagatt 300 ctttgggcta taaagatgaa
gagtctactt cttctggtgc tgatttcaat ctgctgggct 360 gatcatcttt
cagacaacta tactctggat catgacagag ctattcacat ccaagcagaa 420
aatggccccc atctacttgt ggaagcagag caagccaagg tgttttcaca cagaggtggc
480 aatgttacac tgccatgtaa attttatcga gaccctacag catttggctc
aggaatccat 540 aaaatccgaa ttaagtggac caagctaact tcggattacc
tcaaggaagt ggatgttttt 600 gtttccatgg gataccacaa aaaaacctat
ggaggctacc agggtagagt gtttctgaag 660 ggaggcagtg atagtgatgc
ttctctggtc atcacagacc tcactctgga agattatggg 720 agatataagt
gtgaggtgat tgaaggatta gaagatgata ctgttgtggt agcactggac 780
ttacaaggtg tggtattccc ttactttcca cgactggggc gctacaatct caattttcac
840 gaggcgcagc aggcgtgtct ggaccaggat gctgtgatcg cctccttcga
ccagctgtac 900 gacgcctggc ggggcgggct ggactggtgc aatgccggct
ggctcagtga tggctctgtg 960 caatatccca tcacaaagcc cagagagccc
tgtgggggcc agaacacagt gcccggagtc 1020 aggaactacg gattttggga
taaagataaa agcagatatg atgttttctg ttttacatcc 1080 aatttcaatg
gccgttttta ctatctgatc caccccacca aactgaccta tgatgaagcg 1140
gtgcaagctt gtctcaatga tggtgctcag attgcaaaag tgggccagat atttgctgcc
1200 tggaaaattc tcggatatga ccgctgtgat gcgggctggt tggcggatgg
cagcgtccgc 1260 taccccatct ctaggccaag aaggcgctgc agtcctactg
aggctgcagt gcgcttcgtg 1320 ggtttcccag ataaaaagca taagctgtat
ggtgtctact gcttcagagc atacaactga 1380 atgtgccctt agagcgcatc
agttttaaag tcattaagaa catgtgaaag gtgttttttt 1440 tttccaatat
gaactcatgc aagttaccaa aactgtgata accctttttt acttactgta 1500
aagagtcatt ttcataagat caattcattg atttgttttt tgtaaagcta tcattcaata
1560 tatattataa attaatataa atttaaggga agctctatgt aaggagactt
agagccaaac 1620 tgtttaagct gtatcatccc aacaaagtat cctttcatga
acggggcatg caatagctta 1680 agaattgcta ggattaaatt aaggaaagta
aagctactca gagcaacagg ttccacaagc 1740 acaaacttta cacatttgta
caattttgaa atgcactaca ataaacaaat tagagcaaca 1800 catttgaaat
acaggcttct ttacataaac tgagaggtta tacaaaactc agtttcacaa 1860
gggaacaatc tatacctttc taaaagttaa tatttcaagt ctctaatagg cagaatattt
1920 tactctttaa aatcctgcct ttctgaccaa aaaaaaa 1957 63 2166 DNA Homo
sapiens 63 atgttggagc atactactaa gacattcccc ttaagagcac tgcacatagt
tgtggaaagc 60 attagggacc acagtggcca aaaaatgaag caggataaga
aggtggatct tcttgttcca 120 accaaagtga ctggcatcat tacacaagga
gctaaagatt ttggtcatgt acagtttgtt 180 ggctcctaca aactggctta
cagcaatgat ggagaacact ggactgtata ccaggatgaa 240 aagcaaagaa
aagataaggt actgctgggc cggaaggcgg tggtcgtaag ctgcgaaggc 300
atcaacattt ctggcagttt ctgcagaaac aagttgaagt acctggcttt cctccacaag
360 cggatgaaca ccaacccttc tcgacgcccc taccacttcc aggtccccag
ccgcatcttc 420 tggcgacaag aaaaagcaga tggtggttcc tgctgccctc
aaggtcatgc gtctgaagcc 480 tacaagaaag tttgcctatc tggggcgcct
cacgaggttg gctggaagta ccaggcagtg 540 acagccaccc tggaggaaaa
gaggaaagag aaagccgaga tccactaccg gaagaataaa 600 cagctcatga
ggctacagaa acaggccgag aagaacatga agaagaaaat tgacaaatac 660
acagagagtc caggaggagg cagtccccgt ggcttaggct ttatctttaa gacaatagcg
720 ccgctcgccg ccacccgcgc gactcggatc gggcatcccg gcggccgcac
cccgcgcgct 780 ggctcatctg cacaccggcc acctgcattg tcggccagag
cccccgtccc ggcggcttcc 840 ccagcagctt ggctgcccct caggacgccc
tggacccgcc catcctcctg ccccactagc 900 tcatcgactt acgactccct
cagtccctac ggcccacgga accctctccc caacccgcgc 960 cacagcccga
gcggcggcgg cggccttaag aagcccgcaa gacactgtca aggtcaaaag 1020
cacaatgtgc tagccagggg gaaaccccag agaaagccaa aatctgaaaa taacagctgg
1080 tatgtagaaa acggcagacc tgctgacttg gcaggctcag gatattgtgg
tgctctttgg 1140 aaggcaatag agtccttgga ggaaggactt ggaggaaaac
aaaaggacaa ggaaaggaaa 1200 gcagaaaatg gcccccatct acttgtggaa
gcagagcaag ccaaggtgtt ttcacacaga 1260 ggtggcaatg ttacactgcc
atgtaaattt tatcgagacc ctacagcatt tggctcagga 1320 atccataaaa
tccgaattaa gtggaccaag ctaacttcgg attacctcaa ggaagtggat 1380
gtttttgttt ccatgggata ccacaaaaaa acctatggag gctaccaggg tagagtgttt
1440 ctgaagggag gcagtgatag tgatgcttct ctggtcatca cagacctcac
tctggaagat 1500 tatgggagat ataagtgtga ggtgattgaa ggattagaag
atgatactgt tgtggtagca 1560 ctggacttac aaggtgtggt attcccttac
tttccacgac tggggcgcta caatctcaat 1620 tttcacgagg cgcagcaggc
gtgtctggac caggatgctg tgatcgcctc cttcgaccag 1680 ctgtacgacg
cctggcgggg cgggctggac tggtgcaatg ccggctggct cagtgatggc 1740
tctgtgcaat atcccatcac aaagcccaga gagccctgtg gggggcagaa cacagtgccc
1800 ggagtcagga actacggatt ttgggataaa gataaaagca gatatgatgt
tttctgtttt 1860 acatccaatt tcaatggccg tttttactat ctgatccacc
ccaccaaact gacctatgat 1920 gaagcggtgc aagcttgtct caatgatggt
gctcagattg caaaagtggg ccagatattt 1980 gctgcctgga aaattctcgg
atatgaccgc tgtgatgcgg gctggttggc ggatggcagc 2040 gtccgctacc
ccatctctag gccaagaagg cgctgcagtc ctactgaggc tgcagtgcgc 2100
ttcgtgggtt tcccagataa aaagcataag ctgtatggtg tctactgctt cagagcatac
2160 aactga 2166 64 354 PRT Homo sapiens 64 Met Lys Ser Leu Leu Leu
Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp
Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala
Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45
Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50
55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile
Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp
Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly
Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp
Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly
Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr
Val Val Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro
Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175
Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180
185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala
Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys
Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val
Arg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr
Asp Val Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr
Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val
Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly
Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300
Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305
310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe
Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr
Cys Phe Arg Ala 340 345 350 Tyr Asn 65 721 PRT Homo sapiens 65 Met
Leu Glu His Thr Thr Lys Thr Phe Pro Leu Arg Ala Leu His Ile 1 5 10
15 Val Val Glu Ser Ile Arg Asp His Ser Gly Gln Lys Met Lys Gln Asp
20 25 30 Lys Lys Val Asp Leu Leu Val Pro Thr Lys Val Thr Gly Ile
Ile Thr 35 40 45 Gln Gly Ala Lys Asp Phe Gly His Val Gln Phe Val
Gly Ser Tyr Lys 50 55 60 Leu Ala Tyr Ser Asn Asp Gly Glu His Trp
Thr Val Tyr Gln Asp Glu 65 70 75 80 Lys Gln Arg Lys Asp Lys Val Leu
Leu Gly Arg Lys Ala Val Val Val 85 90 95 Ser Cys Glu Gly Ile Asn
Ile Ser Gly Ser Phe Cys Arg Asn Lys Leu 100 105 110 Lys Tyr Leu Ala
Phe Leu His Lys Arg Met Asn Thr Asn Pro Ser Arg 115 120 125 Arg Pro
Tyr His Phe Gln Val Pro Ser Arg Ile Phe Trp Arg Gln Glu 130 135 140
Lys Ala Asp Gly Gly Ser Cys Cys Pro Gln Gly His Ala Ser Glu Ala 145
150 155 160 Tyr Lys Lys Val Cys Leu Ser Gly Ala Pro His Glu Val Gly
Trp Lys 165 170 175 Tyr Gln Ala Val Thr Ala Thr Leu Glu Glu Lys Arg
Lys Glu Lys Ala 180 185 190 Glu Ile His Tyr Arg Lys Asn Lys Gln Leu
Met Arg Leu Gln Lys Gln 195 200 205 Ala Glu Lys Asn Met Lys Lys Lys
Ile Asp Lys Tyr Thr Glu Ser Pro 210 215 220 Gly Gly Gly Ser Pro Arg
Gly Leu Gly Phe Ile Phe Lys Thr Ile Ala 225 230 235 240 Pro Leu Ala
Ala Thr Arg Ala Thr Arg Ile Gly His Pro Gly Gly Arg 245 250 255 Thr
Pro Arg Ala Gly Ser Ser Ala His Arg Pro Pro Ala Leu Ser Ala 260 265
270 Arg Ala Pro Val Pro Ala Ala Ser Pro Ala Ala Trp Leu Pro Leu Arg
275 280 285 Thr Pro Trp Thr Arg Pro Ser Ser Cys Pro Thr Ser Ser Ser
Thr Tyr 290 295 300 Asp Ser Leu Ser Pro Tyr Gly Pro Arg Asn Pro Leu
Pro Asn Pro Arg 305 310 315 320 His Ser Pro Ser Gly Gly Gly Gly Leu
Lys Lys Pro Ala Arg His Cys 325 330 335 Gln Gly Gln Lys His Asn Val
Leu Ala Arg Gly Lys Pro Gln Arg Lys 340 345 350 Pro Lys Ser Glu Asn
Asn Ser Trp Tyr Val Glu Asn Gly Arg Pro Ala 355 360 365 Asp Leu Ala
Gly Ser Gly Tyr Cys Gly Ala Leu Trp Lys Ala Ile Glu 370 375 380 Ser
Leu Glu Glu Gly Leu Gly Gly Lys Gln Lys Asp Lys Glu Arg Lys 385 390
395 400 Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys
Val 405 410 415 Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys
Phe Tyr Arg 420 425 430 Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys
Ile Arg Ile Lys Trp 435 440 445 Thr Lys Leu Thr Ser Asp Tyr
Leu Lys Glu Val Asp Val Phe Val Ser 450 455 460 Met Gly Tyr His Lys
Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val Phe 465 470 475 480 Leu Lys
Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp Leu 485 490 495
Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly Leu 500
505 510 Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val
Phe 515 520 525 Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe
His Glu Ala 530 535 540 Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile
Ala Ser Phe Asp Gln 545 550 555 560 Leu Tyr Asp Ala Trp Arg Gly Gly
Leu Asp Trp Cys Asn Ala Gly Trp 565 570 575 Leu Ser Asp Gly Ser Val
Gln Tyr Pro Ile Thr Lys Pro Arg Glu Pro 580 585 590 Cys Gly Gly Gln
Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe Trp 595 600 605 Asp Lys
Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn Phe 610 615 620
Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr Asp 625
630 635 640 Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala
Lys Val 645 650 655 Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr
Asp Arg Cys Asp 660 665 670 Ala Gly Trp Leu Ala Asp Gly Ser Val Arg
Tyr Pro Ile Ser Arg Pro 675 680 685 Arg Arg Arg Cys Ser Pro Thr Glu
Ala Ala Val Arg Phe Val Gly Phe 690 695 700 Pro Asp Lys Lys His Lys
Leu Tyr Gly Val Tyr Cys Phe Arg Ala Tyr 705 710 715 720 Asn 66 354
PRT Homo sapiens 66 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile
Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp His
Asp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu
Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly
Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr
Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr
Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90 95
Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100
105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr
Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val
Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp
Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly
Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys Leu
Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr Asp
Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp Leu
Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220
Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225
230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr
Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr
Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp
Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp
Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala
Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg Arg
Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe
Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345
350 Tyr Asn 67 721 PRT Homo sapiens 67 Met Leu Glu His Thr Thr Lys
Thr Phe Pro Leu Arg Ala Leu His Ile 1 5 10 15 Val Val Glu Ser Ile
Arg Asp His Ser Gly Gln Lys Met Lys Gln Asp 20 25 30 Lys Lys Val
Asp Leu Leu Val Pro Thr Lys Val Thr Gly Ile Ile Thr 35 40 45 Gln
Gly Ala Lys Asp Phe Gly His Val Gln Phe Val Gly Ser Tyr Lys 50 55
60 Leu Ala Tyr Ser Asn Asp Gly Glu His Trp Thr Val Tyr Gln Asp Glu
65 70 75 80 Lys Gln Arg Lys Asp Lys Val Leu Leu Gly Arg Lys Ala Val
Val Val 85 90 95 Ser Cys Glu Gly Ile Asn Ile Ser Gly Ser Phe Cys
Arg Asn Lys Leu 100 105 110 Lys Tyr Leu Ala Phe Leu His Lys Arg Met
Asn Thr Asn Pro Ser Arg 115 120 125 Arg Pro Tyr His Phe Gln Val Pro
Ser Arg Ile Phe Trp Arg Gln Glu 130 135 140 Lys Ala Asp Gly Gly Ser
Cys Cys Pro Gln Gly His Ala Ser Glu Ala 145 150 155 160 Tyr Lys Lys
Val Cys Leu Ser Gly Ala Pro His Glu Val Gly Trp Lys 165 170 175 Tyr
Gln Ala Val Thr Ala Thr Leu Glu Glu Lys Arg Lys Glu Lys Ala 180 185
190 Glu Ile His Tyr Arg Lys Asn Lys Gln Leu Met Arg Leu Gln Lys Gln
195 200 205 Ala Glu Lys Asn Met Lys Lys Lys Ile Asp Lys Tyr Thr Glu
Ser Pro 210 215 220 Gly Gly Gly Ser Pro Arg Gly Leu Gly Phe Ile Phe
Lys Thr Ile Ala 225 230 235 240 Pro Leu Ala Ala Thr Arg Ala Thr Arg
Ile Gly His Pro Gly Gly Arg 245 250 255 Thr Pro Arg Ala Gly Ser Ser
Ala His Arg Pro Pro Ala Leu Ser Ala 260 265 270 Arg Ala Pro Val Pro
Ala Ala Ser Pro Ala Ala Trp Leu Pro Leu Arg 275 280 285 Thr Pro Trp
Thr Arg Pro Ser Ser Cys Pro Thr Ser Ser Ser Thr Tyr 290 295 300 Asp
Ser Leu Ser Pro Tyr Gly Pro Arg Asn Pro Leu Pro Asn Pro Arg 305 310
315 320 His Ser Pro Ser Gly Gly Gly Gly Leu Lys Lys Pro Ala Arg His
Cys 325 330 335 Gln Gly Gln Lys His Asn Val Leu Ala Arg Gly Lys Pro
Gln Arg Lys 340 345 350 Pro Lys Ser Glu Asn Asn Ser Trp Tyr Val Glu
Asn Gly Arg Pro Ala 355 360 365 Asp Leu Ala Gly Ser Gly Tyr Cys Gly
Ala Leu Trp Lys Ala Ile Glu 370 375 380 Ser Leu Glu Glu Gly Leu Gly
Gly Lys Gln Lys Asp Lys Glu Arg Lys 385 390 395 400 Ala Glu Asn Gly
Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys Val 405 410 415 Phe Ser
His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr Arg 420 425 430
Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys Trp 435
440 445 Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val
Ser 450 455 460 Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly
Arg Val Phe 465 470 475 480 Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser
Leu Val Ile Thr Asp Leu 485 490 495 Thr Leu Glu Asp Tyr Gly Arg Tyr
Lys Cys Glu Val Ile Glu Gly Leu 500 505 510 Glu Asp Asp Thr Val Val
Val Ala Leu Asp Leu Gln Gly Val Val Phe 515 520 525 Pro Tyr Phe Pro
Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu Ala 530 535 540 Gln Gln
Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp Gln 545 550 555
560 Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly Trp
565 570 575 Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg
Glu Pro 580 585 590 Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn
Tyr Gly Phe Trp 595 600 605 Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe
Cys Phe Thr Ser Asn Phe 610 615 620 Asn Gly Arg Phe Tyr Tyr Leu Ile
His Pro Thr Lys Leu Thr Tyr Asp 625 630 635 640 Glu Ala Val Gln Ala
Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys Val 645 650 655 Gly Gln Ile
Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys Asp 660 665 670 Ala
Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg Pro 675 680
685 Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly Phe
690 695 700 Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg
Ala Tyr 705 710 715 720 Asn
* * * * *
References