Method For Isolating Hepatitis C Virus Peptides

Abstract

Described are methods for isolating Hepatitis C Virus peptides (HPs) that have a binding capacity to a MHC/HLA molecule or a complex comprising the HCV-peptide and the MHC/HLA molecule. In one aspect, these methods include providing a pool of HCV-peptide, said pool containing HCV-peptides which bind to said MHC/HLA molecule and HCV-peptides which do not bind to said MHC/HLA molecule, contacting said MHC/HLA molecule with said pool of HCV-peptides whereby a HCV-peptide which has a binding capacity to said MHC/HLA molecule binds to said MHC/HLA molecule and a complex comprising said HCV-peptide and said MHC/HLA molecule is formed, detecting and optionally separating said complex from the HCV-peptide which do not bind to said MHC/HLA molecule and optionally isolating and characterizing the HCV-peptide from said complex. Also described are immunogenic compositions that stimulate a specific T cell response to hepatitis C virus when administered to a subject in an effective amount.

Description

[0001] This application is a continuation of U.S. application Ser. No. 10/512,885, filed Oct. 28, 2004, which is a national phase application under 35 U.S.C. .sctn. 371 of International Application No. PCT/EP2003/009482 filed 27 Aug. 2003, which claims priority to Austrian Application No. A 1376/2002 filed 13 Sep. 2002, International Application No. PCT/EP03/02005 filed 27 Feb. 2003, and European Patent Application No. 03450171.8 filed 11 Jul. 2003, the contents of all of which applications are incorporated herein by reference in their entirety.

[0002] The present invention relates to a method for isolating HCV-peptides, especially for isolating HCV T cell epitopes which have a binding capacity to a MHC/HLA molecule.

[0003] The immune system is a complex network of inter-related cell types and molecules, which has evolved in order to protect multicellular organisms from infectious microorganisms. It can be divided into the evolutionary older innate (or natural) immunity and adaptive (or acquired) immunity. The innate immune system recognizes patterns, which are usually common and essential for pathogens. For this limited number of molecular structures germ-line encoded receptors have evolved. By contrast, cells of the adaptive immune system--B and T lymphocytes--can recognize a huge variety of antigenic structures. The receptors, termed according to the cell types expressing them, B cell receptor (BCR, its soluble versions are called antibodies) and T cell receptor (TCR, only cell-surface associated forms) are generated by somatic recombination and show a clonal distribution. Thus, initially there is only small number of cells with a certain specificity. Upon antigen encounter these cells start to divide (clonal expansion) to generate an effector population able to cope with the antigen. After elimination of antigen a specialized sub-population of cells specifically recognizing this antigen remains as immunological memory. Taken together the adaptive immune system is slow (compared to innate immunity), however specific and it improves upon repeated exposure to a given pathogen/antigen.

[0004] T cells have a central role in adaptive immunity. Their receptors (TCRs) recognize "major histocompatibility complex" (MHC or HLA):peptide complexes on the surface of cells. These peptides are called T cell epitopes and represent degradation products of antigens. There are two major classes of T cells: CD8-positive cytotoxic T cells (CTL) are restricted to MHC class I. CD4-positive helper T cells (HTL) are restricted to MHC class II. HTL are essential for many features of adaptive immunity: activation of so called "professional antigen-presenting cells" (APCs), immunoglobulin (Ig) class switch, the germinal center reaction and Ig affinity maturation, activation of CTL, immunological memory, regulation of the immune response and others.

[0005] MHC molecules collect peptides inside the cell and present them on the cell surface to TCRs of T cells. There are two major classes of MHC, class I recognized by CD8-positive CTL and class II recognized by CD4-positive HTL.

[0006] MHC class I molecules consist of a membrane-anchored alpha-chain of 45 kDa and the non-covalently attached b2-microglobulin (b2m) of 12 kDA. Resolution of the 3-dimensional structure by X-ray crystallography (Stern and Wiley 1994) revealed that the alpha-chain possesses a cleft, which is closed at both ends and accommodates peptides from 8 to 11 amino acids length. Class I molecules are ubiquitously expressed, and the peptides they present originate from cytoplasmic proteins. These are degraded by the proteasome, and the resulting peptides are actively transported into the endoplasmatic reticulum (ER). There, with the help of several chaperones, MHC:peptide complexes are formed and transported to the cell surface (Heemels 1995). Thus, MHC class I mirrors the proteome of a cell on its surface and allows T cells to recognize intracellular pathogens or malignant cells.

[0007] MHC class II molecules consist of two membrane-anchored proteins (alpha- and beta-chain) of 35 kDa and 30 kDa, respectively. These together form a cleft, open at both ends, which can accommodate peptides of variable length, usually from 12 to 25 amino acids. Despite these differences, class I and II molecules share surprising structural similarity (Stern and Wiley 1994). Class II molecules are only expressed on professional APC including dendritic cells (DC), B-cells and macrophages/monocytes. These cells are specialized in taking up and processing antigens in the endosomal pathway. Immediately after their biosynthesis, class II molecules are complexed by the so-called invariant chain (Ii), which prevents binding of peptides in the ER. When vesicles containing class II:Ii complexes fuse with endosomes containing degradation products of exogenous antigen, Ii is degraded until the MHC binding cleft is only complexed by the so-called CLIP peptide. The latter is with the help of chaperones like HLA-DM exchanged by antigenic peptides (Villadangos 2000). Finally, MHC:peptide complexes are again presented on the surface of APCs, which interact in numerous ways with HTL.

[0008] Being both polygenic and extremely polymorphic, the MHC system is highly complex. For the class I alpha-chain in humans there are three gene loci termed HLA-A, -B and -C. Likewise, there are three class II alpha-chain loci (DRA, DQA, DPA); for class II beta-chain loci the situation is even more complex as there are four different DR beta-chains (DRB1,2,3,5) plus DQB and DPB. Except the monomorphic DR alpha-chain DRA, each gene locus is present in many different alleles (dozens to hundreds) in the population (Klein 1986). Different alleles have largely distinct binding specificities for peptides. Alleles are designated, for example, HLA-A*0201 or HLA-DRB1*0401 or HLA-DPA*0101/DPB*0401.

[0009] T cell epitopes have been identified by a variety of approaches (Van den Eynde 1997). T cell lines and clones have for instance been used to screen cDNA expression libraries for instance in the context of COS cells transfected with the appropriate HLA-molecule. Alternatively, biochemical approaches have been pursued. The latter involved elution of natural ligands from MHC molecules on the surface of target cells, the separation of these peptides by several chromatography steps, analysis of their reactivity with lymphocytes in epitope reconstitution assays and sequencing by mass spectrometry (Wolfel et al. 1994, Cox et al. 1994).

[0010] Recently the advent of highly sensitive cytokine detection assays like the IFN-gamma ELIspot allowed using lymphocytes directly ex vivo for screening of overlapping synthetic peptides (Maecker 2001, Kern 2000, Tobery 2001). Primarily, Kern et al. (1999&2000) used arrays of pools of overlapping 9mer peptides to map CD8+ T cell epitopes in vitro. Later, Tobery et al., 2001 modified this approach and demonstrated that pools containing as many as 64 20mer peptides may be used to screen for both CD8+ and CD4+ T cell epitopes in mice. Both these methods were based on the monitoring of antigen-specific response by measuring INF-gamma production either by intracellular staining (Kern et al 2000) or in ELIspot assay (Tobery et al., 2001). By use of mixtures of 15-mers the CD4+ T cell responses are approximately equal to those detected when whole soluble protein was used as an antigen, while--not surprising--the CD8+ T cell responses are significantly higher than the often negligible responses detected with soluble protein stimulation. Furthermore, the CD8+ T cell responses to a mixture of 15 amino acid peptides are similar to those obtained with a mix of 8-12 amino acid peptides, selected to represent known MHC class I minimal epitopes. Most probably peptidases associated with the cell membrane are responsible for "clipping" peptides to optimal length under these circumstances (Maecker et al, 2001).

[0011] An interesting alternative is to screen synthetic combinatorial peptide libraries with specific lymphocytes. For instance, a decapeptide library consisting of 200 mixtures arranged in a positional scanning format, has been successfully used for identification of peptide ligands that stimulate clonotypic populations of T cells (Wilson, et al., J. Immunol., 1999, 163:6424-6434).

[0012] Many T cell epitopes have been identified by so called "Reverse immunological approaches" Rammensee 1999). In this case the protein giving rise to a potential T cell epitope is known, and its primary sequence is scanned for HLA binding motifs. Typically dozens to hundreds of candidate peptides or even a full set of overlapping peptides are synthesized and tested for binding to HLA molecules. Usually, the best binders are selected for further characterization with regard to their reactivity with T cells. This can for instance be done by priming T cells in vitro or in vivo with the help of HLA transgenic mice.

[0013] Hepatitis C Virus (HCV) is a member of the flaviviridiae chronically infecting about 170 million people worldwide. There are at least 6 HCV genotypes and more than 50 subtypes have been described. In America, Europe and Japan genotypes 1, 2 and 3 are most common. The geographic distribution of HCV genotypes varies greatly with genotype 1a being predominant in the USA and parts of Western Europe, whereas 1b predominates in Southern and Central Europe (Bellentani 2000).

[0014] HCV is transmitted through the parenteral or percutan route, and replicates in hepatocytes. About 15% of patients experience acute self-limited hepatitis associated with viral clearance and recovery. About 80% of infected persons become chronic carriers. Infection often persists asymptomatically with slow progression for years, however ultimately HCV is a major cause of cirrhosis, end-stage liver disease and liver cancer (Liang 2000). Strength and quality of both HTL and CTL responses determine whether patients recover (spontaneously or as a consequence of therapy) or develop chronic infection (Liang 2000).

[0015] Standard therapy of HCV comprises a combination of pegylated interferon-alpha and the antiviral ribavirin. Virologic responses are, depending on the genotype, achieved in about 50% of HCV patients. The low tolerability and the considerable side effects of this therapy clearly necessitate novel therapeutic intervention including therapeutic vaccines (Cornberg 2002). However, presently the detailed understanding of which epitopes in which MHC combination lead to successful immune responses is lacking (Ward 2002). Therefore, a comprehensive analysis of the T-cell response against the entire HCV is required for development of therapeutic epitope-based vaccines.

[0016] The HCV virion contains a 9.5-kilobase positive single-strand RNA genome encoding a large single polyprotein of about 3000 amino acids. The latter is processed to at least 10 proteins by both host and HCV-enoded proteolytic activities (Liang 2000). Importantly, the HCV RNA-dependent RNA polymerase is error prone giving rise to the evolution of viral quasispecies and contributing to immune-escape variants (Farci 2000).

[0017] It is an object of the present invention to provide a method for screening HCV-peptides for specific MHC molecules, preferably for delivering suitable and specific HCV T cell epitopes selected from a variety of HCV-peptides having unknown specificity for a given MHC molecule and thereby to provide efficient means for preventing and combatting HCV infections.

[0018] Therefore the present invention provides a method for isolating HCV-peptides which have a binding capacity to a MHC/HLA molecule or a complex comprising said HCV-peptide and said MHC/HLA molecule which method comprises the following steps: [0019] providing a pool of HCV-peptides, said pool containing HCV-peptides which bind to said MHC/HLA molecule and HCV-peptides which do not bind to said MHC/HLA molecule, [0020] contacting said MHC/HLA molecule with said pool of HCV-peptides whereby a HCV-peptide which has a binding capacity to said MHC/HLA molecule binds to said MHC/HLA molecule and a complex comprising said HCV-peptide and said MHC/HLA molecule is formed, [0021] detecting and optionally separating said complex from the HCV-peptides which do not bind to said MHC/HLA molecule and [0022] optionally isolating and characterising the HCV-peptide from said complex.

[0023] The present invention also provides a method for isolating HCV T cell epitopes which have a binding capacity to a MHC/HLA molecule or a complex comprising said epitope and said MHC/HLA molecule which method comprises the following steps: [0024] providing a pool of HCV-peptides, said pool containing HCV-peptides which bind to a MHC/HLA molecule and HCV-peptides which do not bind to said MHC/HLA molecule, [0025] contacting said MHC/HLA molecule with said pool of HCV-peptides whereby a HCV-peptide which has a binding capacity to said MHC/HLA molecule binds to said MHC/HLA molecule and a complex comprising said HCV-peptide and said MHC/HLA molecule is formed, [0026] detecting and optionally separating said complex from the HCV-peptides which do not bind to said MHC/HLA molecule, [0027] optionally isolating and characterising the HCV-peptide from said complex, [0028] assaying said optionally isolated HCV-peptide or said complex in a T cell assay for T cell activation capacity and [0029] providing the optionally isolated HCV-peptide with a T cell activation capacity as HCV T cell epitope or as complex.

[0030] The method according to the present invention enables a screening system for screening binding capacity to specific MHC/HLA molecules. Identifying MHC binding molecules is an important tool for molecular characterisation of pathogens, tumors, etc. It is therefore possible with the present invention to screen a variety (a "pool") of potential HCV-peptides as ligands at once for their functional affinity towards MHC molecules. Binding affinity towards MHC molecules is also a necessary prerequisite for HCV-peptides intended to be used as T cell epitopes, although not a sufficient one. Suitable HCV T cell epitope candidates have also to be screened and assayed with respect to their T cell activation capacity. The combination of the screening method for binding according to the present invention with a suitable T cell assay therefore provides the method for isolating HCV T cell epitopes according to the present invention wherein such T cell epitopes are identifiable out of a pool of potential HCV-peptides using an MHC binding assay.

[0031] In contrast to the prior art, where such assays have always been performed on ligands with known binding/MHC specificity, the methods according to the present invention provide such assays as a screening tool for pools with ligands of unknown specificity. In the prior art such assays have been typically performed on individual single ligands, to test their binding affinity to MHC/HLA molecules. In Kwok et al. (2001) pools of maximally up to 5 overlapping synthetic peptides were used to generate MHC class II tetramers; the latter were then used to stain PBMC for T cells specific for particular MHC class II:peptide complexes which were generated in the binding reaction with the pools of 5 peptides. However, an increase in the number of ligands per pool in such an approach was not regarded as being possible, both for sensitivity and specificity reasons (Novak et al. 2001). A problem with regard to specificity would be the generation of MHC tetramers with more then one binder per tetramer, if more than one binder would be present in the pool. This would preclude staining of T cells, which is used for identification of epitopes in the approach described in the prior art. In strong contrast to that the approach according to the present invention allows the identification of more than on binder out of highly complex mixtures containing more than one binder.

[0032] The nature of the pool to be screened with the present invention is not critical: the pools may contain any naturally or not naturally occurring HCV-peptide which a) binds specifically to MHC/HLA molecules and/or b) may be specifically recognized by T cells. The binding properties of the set of HCV-peptides of the pool with respect to MHC molecules is not known; therefore, usually binders and at least a non-binder for a given MHC molecule are contained in the pool. The pool therefore comprises at least ten different HCV-peptides. Practically, pools are used according to the present invention containing significantly more different HCV-peptide species, e.g. 20 or more, 100 or more, 1.000 or more or 10.000 or more. It is also possible to screen larger libraries (with e.g. more than 10.sup.6, more than 10.sup.8 or even more than 10.sup.10 different HCV-peptide species). This, however, is mainly dependent on the availability of such HCV-peptide libraries.

[0033] Preferred pools of ligands to be used in the method according to the present invention are selected from the group consisting of a pool of peptides, especially overlapping peptides, a pool of protein fragments, a pool of modified peptides, a pool obtained from antigen-presenting cells, preferably in the form of total lysates or fractions thereof, especially fractions eluted from the surface or the MHC/HLA molecules of these cells, a pool comprised of fragments of cells, especially HCV containing cells, tumor cells or tissues, especially from liver, a pool comprised of peptide libraries, pools of (poly)-peptides generated from recombinant DNA libraries, especially derived from pathogens or (liver) tumor cells, a pool of proteins and/or protein fragments from HCV or mixtures thereof.

[0034] The HCV-peptides of the pools may be derived from natural sources (in native and/or derivatised form) but also be produced synthetically (e.g. by chemical synthesis or by recombinant technology). If (poly)peptide ligands are provided in the pools, those peptides are preferably generated by peptide synthesizers or by recombinant technology. According to a preferred embodiment, a pool of (poly)peptides may be generated from recombinant DNA libraries, e.g. derived from HCV or HCV containing (tumor) cells, by in vitro translation (e.g. by ribosome display) or by expression through heterologous hosts like E. coli or others.

[0035] The nature of the specific MHC molecules (of course also MHC-like molecules are encompassed by this term) to be selected for the present methods is again not critical. Therefore, these molecules may be selected in principle from any species, especially primates like humans (HLA, see below), chimpanzees, other mammals, e.g. maquaques, rabbits, cats, dogs or rodents like mice, rats, guinea pigs and others, agriculturally important animals like cattle, horses, sheep and fish, although human (or "humanized") molecules are of course preferred for providing vaccines for humans. For providing vaccines for specific animals, especially agriculturally important animals, like cattle, horses, sheep and fish, the use of MHC molecules being specific for these animals is preferred.

[0036] Preferred HLA molecules therefore comprise Class I molecules derived from the HLA-A, -B or -C loci, especially A1, A2, A3, A24, A11, A23, A29, A30, A68; B7, B8, B15, B16, B27, B35, B40, B44, B46, B51, B52, B53; Cw3, Cw4, Cw6, Cw7; Class II molecules derived from the HLA-DP, -DQ or -DR loci, especially DR1, DR2, DR3, DR4, DR7, DR8, DR9, DR11, DR12, DR13, DR51, DR52, DR53; DP2, DP3, DP4; DQ1, DQ3, DQ5, DQ6; and non-classical MHC/HLA and MHC/HLA-like molecules, which can specifically bind ligands, especially HLA-E, HLA-G, MICA, MICB, Qa1, Qa2, T10, T18, T22, M3 and members of the CD1 family.

[0037] According to a preferred embodiment, the methods according to the present invention is characterised in that said MHC/HLA molecules are selected from HLA class I molecules, HLA class II molecules, non classical MHC/HLA and MHC/HLA-like molecules or mixtures thereof, or mixtures thereof.

[0038] Preferably, the optional characterising step of the HCV-peptides of the complex is performed by using a method selected from the group consisting of mass spectroscopy, polypeptide sequencing, binding assays, especially SDS-stability assays, identification of ligands by determination of their retention factors by chromatography, especially HPLC, or other spectroscopic techniques, especially violet (UV), infra-red (IR), nuclear magnetic resonance (NMR), circular dichroism (CD) or electron spin resonance (ESR), or combinations thereof.

[0039] According to a preferred embodiment the method of the present invention is characterised in that it is combined with a cytokine secretion assay, preferably with an Elispot assay, an intracellular cytokine staining, FACS or an ELISA (enzyme-linked immunoassays) (see e.g. Current Protocols in Immunology).

[0040] Preferred T cell assays comprise the mixing and incubation of said complex with isolated T cells and subsequent measuring cytokine secretion or proliferation of said isolated T cells and/or the measuring up-regulation of activation markers, especially CD69, CD38, or down-regulation of surface markers, especially CD3, CD8 or TCR and/or the measuring up-/down-regulation of mRNAs involved in T cell activation, especially by real-time RT-PCR (see e.g. Current Protocols in Immunology, Current Protocols in Molecular Biology).

[0041] Further preferred T cell assays are selected from T cell assays measuring phosphorylation/de-phosphorylation of components downstream of the T cell receptor, especially p56 lck, ITAMS of the TCR and the zeta chain, ZAP70, LAT, SLP-76, fyn, and lyn, T cell assays measuring intracellular Ca.sup.++ concentration or activation of Ca.sup.++-dependent proteins, T cell assays measuring formation of immunological synapses, T cell assays measuring release of effector molecules, especially perforin, granzymes or granulolysin or combinations of such T cell assays (see e.g. Current Protocols in Immunology, Current Protocols in Cell Biology).

[0042] In order to identify the molecular determinants of immune-protection against HCV a specific method of epitope capturing was applied using synthetic peptides representing the conserved parts of HCV genotypes 1, 2 and 3. Focusing on conserved regions ensures broad applicability of the epitopes. Moreover, these regions probably cannot easily be mutated by the virus, thus minimizing the danger of evolution of immune-escape variants.

[0043] With the methods of the present invention novel HCV-epitopes are detected. According to a further aspect, the present invention therefore also provides HCV T cell epitopes identifiable by a method according to the present invention, said T cell epitopes preferably being selected from the group consisting of polypeptides comprising the peptides A120-A124, B25-B30, B46-B48, B84-B92, C106, C113-C114, 1627, 1628, 1629, 1604 according to Table 1 or 2. These peptides are novel ligands for at least HLA-DRB1*0101, *0401, *0404, *0701 and thus covering at least 45-55% of major populations (see Tab. 2).

[0044] Preferred polypeptides are selected from the group comprising the peptides 1630, C97, 1547, B94-B98, A272-A276 according to Table 1 or 2. These peptides are novel ligands for at least HLA-DRB1*0101, *0401, *0701 and thus covering at least 40-50% of major populations (see Tab. 2).

[0045] Preferred polypeptides are selected from the group comprising the peptides B120, B122, C108, C134, C152 according to Table 1 or 2. These peptides are novel ligands for at least HLA-DRB1*0101, *0404, *0701 and thus covering at least 45% of major populations (see Tab. 2).

[0046] Preferred polypeptides are selected from the group comprising the peptides 1606, 1607, 1577, 1578 according to Table 1 or 2. These peptides are novel ligands for at least HLA-DRB1*0401, *0404, *0701 and thus covering at least 45% of major populations (see Tab. 2).

[0047] Preferred polypeptides are selected from the group comprising the peptides B50-52, 1623, C130 according to Table 1 or 2. These peptides are novel ligands for at least HLA-DRB1*0101, *0401, *0404 and thus covering at least 40% of major populations (see Tab. 2).

[0048] Preferred polypeptides are selected from the group comprising the peptides 1603, C96 according to Table 1 or 2. These peptides are novel ligands for at least HLA-DRB1*0101, *0701 and thus covering at least 40% of major populations (see Tab. 2).

[0049] Preferred polypeptides are selected from the group comprising the peptides C191 according to Table 1, being a novel ligand for at least HLA-DRB1*0401, *0701 and thus covering at least 40% of major populations (see Tab. 2).

[0050] Preferred polypeptides are selected from the group comprising the peptides A216-A224, A242-A244, C92-C93 according to Table 1 or 2. These peptides are novel ligands for at least HLA-DRB1*0101, *0401 and thus covering at least 35% of major populations (see Tab. 2).

[0051] Preferred polypeptides are selected from the group comprising the peptide A174 according to Table 1 or 2, being a novel ligand for at least HLA-DRB1*0404, *0701 and thus covering at least 25-30% of major populations (see Tab. 2).

[0052] Preferred polypeptides are selected from the group comprising the peptides B32-B38, B100-B102, C135 according to Table 1 or 2. These peptides are novel ligands for at least HLA-DRB1*0101, *0404 and thus covering at least 20-25% of major populations (see Tab. 2).

[0053] Preferred polypeptides are selected from the group comprising the peptide C162 according to Table 1 or 2, being a novel ligand for at least HLA-DRB1*0401, *0404 and thus covering at least 20-25% of major populations (see Tab. 2).

[0054] Preferred polypeptides are selected from the group comprising the peptides 1618, 1622, 1624, 1546, 1556 according to Table 1 or 2. These peptides are novel ligands for at least HLA-DRB1*0701 and thus covering at least 25% of major populations (see Tab. 2).

[0055] Preferred polypeptides are selected from the group comprising the peptides A114, B58, B112-B118, B18-B22, C112, C116, C122, C127, C144, C159-C160, C174, 1558, 1581 according to Table 1 or 2. These peptides are novel ligands for at least HLA-DRB1*0101 and thus covering at least 20% of major populations (see Tab. 2).

[0056] Preferred polypeptides are selected from the group comprising the peptide C95, being a novel ligand for at least HLA-DRB1*0401 and thus covering at least 20% of major populations (see Tab. 2).

[0057] Preferred polypeptides are selected from the group comprising the peptides C129, C157-C158, A254-A258, 1605, C109, C161 according to Table 1 or 2. These peptides comprising novel ligands for at least HLA-DRB1*0404 and thus covering at least 5% of major populations (see Tab. 2).

[0058] Preferred polypeptides are selected from the group comprising the peptides 1547, 1555, 1558, 1559, 1560, 1563, 1592, 1604, 1605, 1616, 1621, 1623, 1625, 1627, 1630, 1649, 1650, 1651, 1652, 1654, 1655, 1656 according to Table 1 or 2, these peptides displaying immunogenicity in HLA-DRB1*0401 transgenic mice (see Example II) and thus representing or containing a confirmed HLA class II T-cell epitope binding to at least HLA-DRB1*0401 (see Tab. 3).

[0059] Preferred polypeptides are selected from the group comprising the peptides 1545, 1552, 1555, 1558, 1559, 1560, 1577, 1592, 1604, 1605, 1615, 1617, 1621, 1627, 1631, 1632, 1641, 1647, 1650, 1651, 1652, 1653, 1654, 1655 according to Table 1 or 2, these peptides displaying immunogenicity in HLA-A*0201 transgenic mice (see Example II) and thus representing or containing a confirmed HLA class I T-cell epitope binding to at least HLA-A*0201 (see Tab. 3).

[0060] Preferred polypeptides which are shown to be HLA-B*0702 epitopes with T-cell activating capacity are selected from the group consisting of polypeptides 1506, 1526, 1547, 1552, 1553, 1555, 1558, 1562, 1563, 1565, 1577, 1578, 1580, 1587, 1592, 1604, 1605, 1621, 1623, 1624, 1627, 1628, 1647, 1650, 1651, 1843 with sequence LPRRGPRL (SEQ ID NO:163) (contained in 1506) and 1838 with sequence SPGALVVGVI (SEQ ID NO:164) (contained in 1587) as minimal HLA-B*0702 epitopes.

[0061] Peptides 1526, 1565, 1631 are also shown to be immunogenic in HLA-DRB1*0401 transgenic mice contain known class II epitopes. Peptides 1526, 1553, 1565, 1587, 1623, 1630 are also shown to be immunogenic in HLA-A*0201 transgenic mice contain known A2 epitopes.

[0062] Preferred polypeptides are selected from the group comprising the peptides listed in tables 3, 5 and the bold peptides in 7 ("hotspots").

[0063] The preferred polypeptides mentioned above also include all fragments containing the minimal sequence of the epitope, i.e. the 8- or 9-mer being necessary for binding to MHC/HLA molecules.

[0064] Preferably, the epitopes or peptides according to the present invention further comprises 1 to 30, preferably 2 to 10, especially 2 to 6, naturally occurring amino acid residues at the N-terminus, the C-terminus or at the N- and C-terminus. For the purposes of the present invention the term "naturally occurring" amino acid residue relates to amino acid residues present in the naturally occurring protein at the specific position, relative to the epitope or peptide. For example, for the HLA-A2 epitope with the amino acid sequence HMWNFISGI (SEQ ID NO:192) contained within peptide ID 1565 (Tab. 1), the naturally occurring amino acid residue at the N-terminus is -K; the three naturally occurring amino acid residues at the C-terminus are -QYL. A "non-naturally occurring" amino acid residue is therefore any amino acid residue being different as the amino acid residue at the specific position relative to the epitope or peptide.

[0065] According to a preferred embodiment of the present invention, the present epitopes or peptides further comprise non-naturally occurring amino acid(s), preferably 1 to 1000, more preferred 2 to 100, especially 2 to 20 non-naturally occurring amino acid residues, especially at the N-terminus, the C-terminus or at the N- and C-terminus. Also combinations of non-naturally and naturally occurring amino acid residues are possible under this specific preferred embodiment. The present epitope may also contain modified amino acids (i.e. amino acid residues being different from the 20 "classical" amino acids, such as D-amino acids or S-S bindings of Cys) as additional amino acid residues or in replacement of a naturally occurring amino acid residue.

[0066] It is clear that also epitopes or peptides derived from the present epitopes or peptides by amino acid exchanges improving, conserving or at least not significantly impeding the T cell activating capability of the epitopes are covered by the epitopes or peptides according to the present invention. Therefore, the present epitopes or peptides also cover epitopes or peptides, which do not contain the original sequence as derived from a specific strain of HCV, but trigger the same or preferably an improved T cell response. These epitopes are referred to as "heteroclitic". These include any epitope, which can trigger the same T cells as the original epitope and has preferably a more potent activation capacity of T cells preferably in vivo or also in vitro. Also the respective homologous epitopes from other strains of HCV are encompassed by the present invention.

[0067] Heteroclitic epitopes can be obtained by rational design i.e. taking into account the contribution of individual residues to binding to MHC/HLA as for instance described by Ramensee et al. 1999 or Sturniolo et al. 1999, combined with a systematic exchange of residues potentially interacting with the TCR and testing the resulting sequences with T cells directed against the original epitope. Such a design is possible for a skilled man in the art without much experimentation.

[0068] Another possibility includes the screening of peptide libraries with T cells directed against the original epitope. A preferred way is the positional scanning of synthetic peptide libraries. Such approaches have been described in detail for instance by Blake et al 1996 and Hemmer et al. 1999 and the references given therein.

[0069] As an alternative to epitopes represented by the cognate HCV derived amino acid sequence or heteroclitic epitopes, also substances mimicking these epitopes e.g. "peptidemimetica" or "retro-inverso-peptides" can be applied.

[0070] Another aspect of the design of improved epitopes is their formulation or modification with substances increasing their capacity to stimulate T cells. These include T helper cell epitopes, lipids or liposomes or preferred modifications as described in WO 01/78767.

[0071] Another way to increase the T cell stimulating capacity of epitopes is their formulation with immune stimulating substances for instance cytokines or chemokines like interleukin-2, -7, -2, -18, class I and II interferons (IFN), especially IFN-gamma, GM-CSF, TNF-alpha, flt3-ligand and others.

[0072] According to a further aspect, the present invention is drawn to the use of a HCV epitope or HCV peptide according to the present invention for the preparation of a HLA restricted vaccine for treating or preventing hepatitis C virus (HCV) infections.

[0073] The invention also encompasses the use of an epitope according to the present invention for the preparation of a vaccine for treating or preventing hepatitis C virus (HCV) infections.

[0074] Consequently, the present invention also encompasses a vaccine for treating or preventing hepatitis C virus (HCV) infections comprising an epitope according to the present invention.

[0075] Furthermore, also a HLA specific vaccine for treating or preventing hepatitis C virus (HCV) infections comprising the epitopes or peptides according to the present invention is an aspect of the present invention.

[0076] Preferably, such a vaccine further comprises an immunomodulating substance, preferably selected from the group consisting of polycationic substances, especially polycationic polypeptides, immunomodulating nucleic acids, especially deoxyinosine and/or deoxyuracile containing oligodeoxynucleotides, or mixtures thereof.

[0077] Preferably the vaccine further comprises a polycationic polymer, preferably a polycationic peptide, especially polyarginine, polylysine or an antimicrobial peptide.

[0078] The polycationic compound(s) to be used according to the present invention may be any polycationic compound, which shows the characteristic effect according to the WO 97/30721. Preferred polycationic compounds are selected from basic polypeptides, organic polycations, basic polyaminoacids or mixtures thereof. These polyaminoacids should have a chain length of at least 4 amino acid residues. Especially preferred are substances containing peptidic bounds, like polylysine, polyarginine and polypeptides containing more than 20%, especially more than 50% of basic amino acids in a range of more than 8, especially more than 20, amino acid residues or mixtures thereof. Other preferred polycations and their pharmaceutical compositions are described in WO 97/30721 (e.g. polyethyleneimine) and WO 99/38528. Preferably these polypeptides contain between 20 and 500 amino acid residues, especially between 30 and 200 residues.

[0079] These polycationic compounds may be produced chemically or recombinantly or may be derived from natural sources.

[0080] Cationic (poly)peptides may also be polycationic anti-bacterial microbial peptides. These (poly)peptides may be of prokaryotic or animal or plant origin or may be produced chemically or recombinantly. Peptides may also belong to the class of defensines. Such host defense peptides or defensines are also a preferred form of the polycationic polymer according to the present invention. Generally, a compound allowing as an end product activation (or down-regulation) of the adaptive immune system, preferably mediated by APCs (including dendritic cells) is used as polycationic polymer.

[0081] Especially preferred for use as polycationic substance in the present invention are cathelicidin derived antimicrobial peptides or derivatives thereof (WO 02/13857), incorporated herein by reference), especially antimicrobial peptides derived from mammal cathelicidin, preferably from human, bovine or mouse, or neuroactive compounds, such as (human) growth hormone (as described e.g. in WO01/24822).

[0082] Polycationic compounds derived from natural sources include HIV-REV or HIV-TAT (derived cationic peptides, antennapedia peptides, chitosan or other derivatives of chitin) or other peptides derived from these peptides or proteins by biochemical or recombinant production. Other preferred polycationic compounds are cathelin or related or derived substances from cathelin, especially mouse, bovine or especially human cathelins and/or cathelicidins. Related or derived cathelin substances contain the whole or parts of the cathelin sequence with at least 15-20 amino acid residues. Derivations may include the substitution or modification of the natural amino acids by amino acids, which are not among the 20 standard amino acids. Moreover, further cationic residues may be introduced into such cathelin molecules. These cathelin molecules are preferred to be combined with the antigen/vaccine composition according to the present invention. However, these cathelin molecules surprisingly have turned out to be also effective as an adjuvant for a antigen without the addition of further adjuvants. It is therefore possible to use such cathelin molecules as efficient adjuvants in vaccine formulations with or without further immunactivating substances.

[0083] Another preferred polycationic substance to be used according to the present invention is a synthetic peptide containing at least 2 KLK-motifs separated by a linker of 3 to 7 hydrophobic amino acids, especially L (WO 02/32451, incorporated herein by reference).

[0084] The immunomodulating (or:immunogenic) nucleic acids to be used according to the present invention can be of synthetic, prokaryotic and eukaryotic origin. In the case of eukaryotic origin, DNA should be derived from, based on the phylogenetic tree, less developed species (e.g. insects, but also others). In a preferred embodiment of the invention the immunogenic oligodeoxynucleotide (ODN) is a synthetically produced DNA-molecule or mixtures of such molecules. Derivatives or modifications of ODNs such as thiophosphate substituted analogues (thiophosphate residues substitute for phosphate) as for example described in US patents U.S. Pat. No. 5,723,335 and U.S. Pat. No. 5,663,153, and other derivatives and modifications, which preferably stabilize the immunostimulatory composition(s) but do not change their immunological properties, are also included. A preferred sequence motif is a six base DNA motif containing an (unmethylated) CpG dinucleotide flanked by two 5' purines and two 3' pyrimidines (5'-Pur-Pur-C-G-Pyr-Pyr-3'). The CpG motifs contained in the ODNs according to the present invention are more common in microbial than higher vertebrate DNA and display differences in the pattern of methylation. Surprisingly, sequences stimulating mouse APCs are not very efficient for human cells. Preferred palindromic or non-palindromic ODNs to be used according to the present invention are disclosed e.g. in Austrian Patent applications A 1973/2000, A 805/2001, EP 0 468 520 A2, WO 96/02555, WO 98/16247, WO 98/18810, WO 98/37919, WO 98/40100, WO 98/52581, WO 98/52962, WO 99/51259 and WO 99/56755 all incorporated herein by reference. Apart from stimulating the immune system certain ODNs are neutralizing some immune responses. These sequences are also included in the current invention, for example for applications for the treatment of autoimmune diseases. ODNs/DNAs may be produced chemically or recombinantly or may be derived from natural sources. Preferred natural sources are insects.

[0085] Alternatively, also nucleic acids based on inosine and cytidine (as e.g. described in the WO 01/93903) or deoxynucleic acids containing deoxy-inosine and/or deoxyuridine residues (described in WO 01/93905 and PCT/EP 02/05448, incorporated herein by reference) may preferably be used as immunostimulatory nucleic acids for the present invention.

[0086] Of course, also mixtures of different immunogenic nucleic acids may be used according to the present invention.

[0087] Preferably, the present vaccine further comprises a pharmaceutically acceptable carrier.

[0088] According to a further preferred embodiment, the present vaccine comprises an epitope or peptide which is provided in a form selected from peptides, peptide analogues, proteins, naked DNA, RNA, viral vectors, virus-like particles, recombinant/chimeric viruses, recombinant bacteria or dendritic cells pulsed with protein/peptide/RNA or transfected with DNA comprising the epitopes or peptides.

[0089] According to a further aspect, the present invention is drawn to T cells, a T cell clone or a population (preparation) of T cells specifically recognizing any HCV epitope or peptide according to the present invention, especially a HCV epitope as described above. A preferred application of such T cells is their expansion in vitro and use for therapy of patients e.g. by adoptive transfer. Therefore, the present invention also provides the use of T cells, a T cell clone or a population (preparation) of T cells for the preparation of a composition for the therapy of HCV patients.

[0090] Such T cells (clones or lines) according to the present invention, specifically those recognizing the aforementioned HCV peptides are also useful for identification of heteroclitic epitopes, which are distinct from the originally identified epitopes but trigger the same T cells.

[0091] Such cells, compositions or vaccines according to the present invention are administered to the individuals in an effective amount.

[0092] According to a further aspect, the present invention also relates to the use of the peptides with formulae QRKTKRNTN (SEQ ID NO:167), QRKTKRNT (SEQ ID NO:166), or 1615, 1616, 1617 in particular 9meric peptides derived from the latter 3 peptides with formulae SAKSKFGYG (SEQ ID NO:193), SAKSKYGYG (SEQ ID NO:194), or SARSKYGYG (SEQ ID NO:195) as HLA-B*08 epitopes, especially for the preparation of a pharmaceutical preparation for a HLA-B*08 specific vaccine; the use of the peptides with the formulae RKTKRNTNR (SEQ ID NO:170) as HLA-B*2705 epitope, especially for the preparation of a pharmaceutical preparation for a HLA-B*2705 specific vaccine; and the use of the peptides with the formulae ARLIVFPDL (SEQ ID NO:1053) as HLA-B*2705 and HLA-B*2709 specific vaccine. Further, it also relates to the use of the hotspot epitopes selected from the group of peptides 1835, 84EX, 87EX, 89EX, 1426, 1650, 1836, 1846, 1651, 1800, 1799, C114, 1827, C112, C114EX, 1827EX, 1798, 1604, 1829, 1579, 1624, 1848, 1547, A1A7, A122EX, A122, 1825, A241, B8B38, C70EX, C92, C97, C106, and C134 according to table 7 for the preparation of a vaccine comprising synthetic peptides, recombinant protein and/or DNA constitutes of such epitopes.

[0093] In particular, two or more epitope hotspots can be combined, with or without linker sequences. Preferred linker sequences consist for instance of 3 to 5 glycine, or alanine or lysine residues. This may be achieved by peptide synthesis, However, combination of hotspots may result in quite long polypeptides. In this case, cloning DNA encoding for such constructs and expressing and purifying the corresponding recombinant protein

is an alternative. Such recombinant proteins can be used as antigens, which in combination with the right adjuvant (IC31, pR, . . . ) can elicit T-cell responses against all the epitopes they harbor. At the same time, such artificial polypeptides are devoid of the activities (enzymatic, toxic, immuno-suppressive, . . . ), the natural HCV antigens may possess.

[0094] There are several other ways of delivering T-cell epitope hotspots or combinations thereof. These include: recombinant viral vectors like vaccinia virus, canary pox virus, adenovirus; self-replicating RNA vectors; "naked DNA" vaccination with plasmids encoding the hotspots or combination thereof; recombinant bacteria (e.g. Salmonella); dendritic cells pulsed with synthetic peptides, or recombinant protein, or RNA or transfected with DNA, each encoding T-cell epitope hotspots or combinations thereof.

[0095] The invention will be explained in more detail by way of the following examples and drawing figures, to which, however it is not limited.

[0096] FIG. 1 shows 40 peptide mixtures each containing up to 20 HCV derived 15- to 23mer peptides.

[0097] FIG. 2 shows the Epitope Capture approach using peptide pools and empty DRB1*0401 molecules.

[0098] FIG. 3 shows the Epitope Capture approach using peptide pools and empty DRB1*0404 molecules.

[0099] FIG. 4 shows binding of individual peptides to DRB1*0401.

[0100] FIG. 5 shows binding of individual peptides to DRB1*0404.

[0101] FIG. 6 shows binding of individual peptides to DRB1*0101.

[0102] FIG. 7 shows peptides binding to DRB1*0701.

[0103] FIG. 8 shows mouse IFN-gamma ELIspot with splenocytes or separated CD8+ or CD4+ cells from HLA-DRB1*0401 tg mice vaccinated with Ipep1604+IC31.

[0104] FIG. 9 shows mouse IFN-gamma ELIspot with splenocytes or separated CD8+ or CD4+ cells from HLA-A*0201 tg mice vaccinated with Ipep1604+IC31.

[0105] FIG. 10 shows mouse IFN-gamma ELIspot with splenocytes or separated CD8+ or CD4+ cells from HLA-B*0702tg mice vaccinated with Ipep1604+IC31.

EXAMPLES

General Description of the Examples

[0106] The present examples show the performance of the present invention on a specific pathogen hepatitis C virus (HCV).

[0107] In the first part the method according to the present invention was applied, which is based on the use of "empty HLA molecules". These molecules were incubated with mixtures of potential HCV derived peptide ligands, screening for specific binding events. The possibility to use highly complex mixtures allows a very quick identification of the few binders out of hundreds or even thousands of potential ligands. This is demonstrated by using HLA-DRB1*0101, -DRB1*0401, -DRB1*0404, -DRB1*0701 molecules and pools of overlapping 15- to 23mers. Importantly, this analysis using multiple different HLA-alleles allows identifying promiscuous ligands capable to binding to more than one HLA allele. Promiscuous T-cell epitopes are particularly valuable components of epitope-based vaccines. They enable treating a higher portion of a population than epitopes restricted to one HLA allele.

[0108] The same process can be applied for class I molecules and peptides of appropriate length i.e. 8 to 11-mers. The ligand-pools can be synthetic overlapping peptides. Another possibility is to digest the antigen in question enzymatically or non-enzymatically. The latter achieved by alkali-hydrolysis generates all potential degradation products and has been successfully used to identify T cell epitopes (Gavin 1993). Enzymatic digestions can be done with proteases. One rational way would further be to use proteases involved in the natural antigen-processing pathway like the proteasome for class I restricted epitopes (Heemels 1995) or cathepsins for class II restricted epitopes (Villadangos 2000). Ligand pools could also be composed of naturally occurring ligands obtained for instance by lysis of or elution from cells carrying the respective epitope. In this regard it is important to note that also non-peptide ligands like for instance glycolipids can be applied. It is known that nonclassical class I molecules, which can be encoded by the MHC (e.g. HLA-G, HLA-E, MICA, MICB) or outside the MHC (e.g. CD1 family) can present various non-peptide ligands to lymphocytes (Kronenberg 1999). Use of recombinant "empty" nonclassical class I molecules would allow binding reactions and identification of binders in similar manner as described here.

[0109] After rapid identification of ligands capable of binding to HLA molecules the process according to the present invention also offers ways to characterize directly specific T cell responses against these binders. One possibility is to directly use the isolated HLA:ligand complex in a so called "synthetic T cell assay". The latter involves antigen-specific re-stimulation of T cells by the HLA:ligand complex together with a second signal providing co-stimulation like activation of CD28 by an activating antibody. This assay can be done in an ELIspot readout.

[0110] Another possibility is the immunization of HLA-transgenic mice to prove immunogenicity of ligands identified by the Epitope Capture approach as demonstrated in Example II.

Materials & Methods

Peptides

[0111] In order to identify conserved regions between HCV genotypes 1, 2 and 3, about 90 full genomes publicly available through Genebank were aligned. In total, 43% of the coding region of HCV was found to be conserved in at least 80% of clinical isolates. In cases, where at a certain position consistently two distinct amino acids (eg. arginine or lysine) were found, both variants were considered for analysis. Altogether 148 conserved regions, longer than 8 amino acids were identified. Conserved region were spanned by .about.500 fifteen amino acid residue (15mer) peptides, each peptide overlapping its precursor by 14 out of 15 amino acids. Conserved regions between 8 and 14 amino acids long were covered by further 80 (non-overlapping) 15mers. 15mers were synthesized using standard F-moc chemistry in parallel (288 at a time) on a Syro II synthesizer (Multisyntech, Witten, Germany). Each fourth 15mer was checked by mass spectrometry. 15mers were applied for experiments without further purification. In addition 63 peptides of 16-xx aa were synthesized using standard F-moc chemistry on an ABI 433A synthesizer (Applied Biosystems, Weiterstadt, Germany) and purified by RP-HPLC (Biocut 700E, Applied Biosystems, Langen, Germany) using a C18 column (either ODS ACU from YMC or 218TP, Vydac). Purity and identity were characterized by MALDI-TOF on a Reflex III mass-spectrometer (Bruker, Bremen, Germany). Peptides were solubilized in 100% DMSO at .about.10 mg/ml (.about.5 mM). Stocks of peptide pools (20 peptides each) were made in 1000 DMSO at a final concentration of 0.5 mg/ml (.about.0.25 mM) for each peptide. All peptides used in the present invention are listed in Table 1. Peptides YAR (YARFQSQTTLKQKT (SEQ ID NO:196)), HA (PKYVKQNTLKLAT (SEQ ID NO:197)), P1 (GYKVLVLNPSVAAT (SEQ ID NO:198)), P2 (HMWNFISGIQYLAGLSTLPGNPA (SEQ ID NO:199)), P3 (KFPGGGQIVGVYLLPRRRGPRL (SEQ ID NO:200)), P4 (DLMGYIPAV (SEQ ID NO:201)) and CLIP (KLPKPPKPVSKMRMATPLLMQALPM (SEQ ID NO:202)) were used as control peptides in binding assays.

Epitope Capture and Peptide Binding Assay

[0112] Soluble HLA class II DRA1*0101/DRB1*0101/Ii, DRA1*0101/DRB1*0401/Ii, DRA1*0101/DRB1*0404/Ii and DRA1*0101/DRB1*0701/Ii molecules were expressed in SC-2 cells and purified as described in Aichinger et al., 1997. In peptide binding reactions soluble DRB1*0101, DRB1*0401, DRB1*0404 molecules were used in a concentration of .about.0.5 .mu.M, and each single peptide was added in 10-fold molar excess (5 .mu.M) if not mentioned differently. The concentration of DMSO in the binding reaction did not exceed 4%. The reaction was performed in PBS buffer (pH 7.4) at room temperature for 48 hours in the presence of a protease inhibitor cocktail (Roche) and 0.1% octyl-beta-D-glucopyranoside (Sigma). Peptide binding was evaluated in an SDS-stability assay (Gorga et al., 1987): trimeric HLA class II alpha:beta:peptide complexes are resistant to SDS and consequently appear as .about.60 kDa band in SDS-PAGE Western blot analysis. Individual HLA class II alpha- and beta-chains not stabilized by bound peptide migrate as .about.35 kDa and 25 kDa bands, respectively. Briefly, HLA-peptide complexes were treated with 1% SDS at room temperature and resolved by SDS-PAGE run with 20 mA for approximately 2.5 hours at room temperature. Protein was transferred onto PVDF membrane by electroblotting, and stained with anti-alpha-chain TAL.1B5 or/and beta-chain MEM136 antibodies. For detection of Western-blot signals ECL solutions (Amersham) were used. For DRB1*0101 molecules HA and P1 peptides were used as controls for evaluation of strong binding, P2 peptide for intermediate binding and YAR as a negative control. For DRB1*0401 the strongest binding controls were YAR and HA peptides, while P1 and P2 served as an intermediate and weak binder, respectively. In the case of DRB1*0404 molecules P1 and P2 peptides were used to estimate strong binding, YAR peptide to control intermediate binding and HA peptide as an negative control. The binding affinities to DRB1*0701 were test by a peptide-competition assay (Reay et al., 1992). Briefly, binding of the biotinylated CLIP peptide with high affinity (reference peptide) has been used for monitoring of HLA:peptide complex formation. A testing peptide added to the binding reaction at an equimolar concentration to CLIP peptide could compete out CLIP when its affinity is higher or inhibit binding for 50% if its affinity is equal to affinity of CLIP. In the case of lower affinity peptides they should be added in excess to the reference peptide to compete for occupancy of HLA binding grove. The values of the concentration of competitor peptides required for 50% inhibition of reference peptide (biotinylated CLIP) binding (IC.sub.50) can be used for evaluation of peptide binding affinities. Alternatively, comparing of the amount of reference peptide bound to HLA molecules in the presence or absence of competitor peptide one can determine the binding activity of the peptide of interest. In the present peptide-competition assay conditions of peptide binding were similar to described above. DRB1*0701 molecules were used in a concentration of .about.0.5 .mu.M and biotinylated CLIP was added to all samples in the final concentration of 2 .mu.M. Competitor peptides were added in three different concentrations: 2 .mu.M, 20 .mu.M and 200 .mu.M. Binding reaction was performed in PBS buffer (pH 7.4) for 18 hours at 37.degree. C. The amount of biotinylated CLIP associated with soluble DRB1*0701 molecules was determined by ELISA. Briefly, MaxiSorp 96-well plates (Nunc, Denmark) were coated with mouse anti-DR antibody L243 by overnight incubation with 50 .mu.l of 10 .mu.g/ml dilution in PBS at 4.degree. C. Non-specific binding to wells awas blocked by incubation with T-PBS containing 3% of BSA for 2 hours at 37.degree. C. and binding reactions were then "captured" for 2 hours at room temperature. Following extensive washing, HLA-associated peptide complexes were detected using alkaline phosphatase-streptavidin (Dako) and Sigma 104 phosphatase substrate. A microplate reader (VICTOR) was used to monitor optical density at 405 nm. Non-biotinylated CLIP, P1 and P2 peptides were used as positive controls to evaluate strong binding. Peptide P3 and P4 served as a weakly binding and non-binding control, respectively.

Immunization of HLA-Transgenic Mice

[0113] Immunogenicity of synthetic HCV-derived peptides was tested in HLA-DRB1*0401- and HLA-A*0201-transgenic mice as follows: Groups of 3 mice (female, 8 weeks of age) were injected subcutaneously into the flank (in total 100 .mu.g of peptide+30 .mu.g oligodinucleotide CpI (Purimex, Gottingen, Germany) per mouse). One week after the vaccination, spleens were removed and the splenocytes were activated ex vivo with the peptide used for vaccination and an irrelevant negative control peptide to determine IFN-gamma-producing specific cells (mouse ELISpot assay).

[0114] Mouse splenocyte ELIspot assay for single cell IFN-gamma release ELISpot plates (MAHA S4510, Millipore, Germany) were rinsed with PBS (200 .mu.l/well), coated with anti-mouse IFN-gamma mAb (clone R46A2; 100 .mu.l/well of 5 .mu.g/ml in 0.1 M NaHCO.sub.3, pH 9.2-9.5) and incubated overnight at 4.degree. C. Plates were washed four times with PBS/0.1% Tween 20 and incubated with PBS/1% BSA (200 .mu.l/well) at room temperature for 2 h to block nonspecific binding. Spleen cells from vaccinated mice were prepared and plated at 1.times.10.sup.6-3.times.10.sup.5 cells/well and incubated overnight at 37.degree. C./5% CO.sub.2 either in the presence of the immunizing antigen (peptide), control peptides or with medium alone. Subsequently, plates were washed four times and incubated with biotinylated anti-mouse IFN-gamma mAb (clone AN18.17.24, 100 .mu.l/well of 2 .mu.g/ml in PBS/1% BSA) for 2 h at 37.degree. C. After washing, streptavidin-peroxidase (Roche Diagnostics, Vienna, Austria) was added ( 1/5000 in PBS, 100 .mu.l/well) and plates were incubated at room temperature for 2 additional hours. Subsequently, substrate was added to the washed plates (100 .mu.l/well of a mixture of 10 ml 100 mM Tris pH 7.5 supplemented with 200 .mu.l of 40 mg/ml DAB stock containing 50 .mu.l of 80 mg/ml NiCl.sub.2 stock and 5 .mu.l of 30% H.sub.2O.sub.2). The reaction was stopped after 20-30 minutes by washing the plates with tap water. Dried plates were evaluated with an ELISpot reader (BIOREADER 2000, BioSys, Karben, Germany).

IFN-Gamma ELIspot with Human PBMC

[0115] PBMC from HCV RNA-negative therapy responders or subjects spontaneously recovered were collected and HLA-typed serologically. Whole blood was collected in ACD Vacutainer tubes (Becton Dickinson Europe, Erembodegem, Germany). PBMC were isolated on Lymphoprep (Nycomed Pharma AS, Oslo, Norway) using Leuco-sep tubes (Greiner, Frickenhausen, Germany), washed 3.times. with PBS (Invitrogen Life Technologies (formerly GIBCOBRL), Carlsbad, Calif., USA) and resuspended at a concentration of 2.times.10.sup.7/ml in freezing medium consisting of 4 parts RPMI 1640 supplemented with 1 mM sodium pyruvate, 2 mM L-glutamine, 0.1 mM non-essential amino acids, 50 .mu.M 2-mercaptoethanol (all from Invitrogen Life Technologies), 9 parts foetal bovine serum (FCS; from PAA, Linz, Austria) and 1 part DMSO (SIGMA, Deisenhofen, Germany). PBMC were stored over night in 1.degree. C. freezing containers (Nalgene Nunc International, Rochester, N.Y., USA) at -80.degree. C. and then transferred into liquid nitrogen. The ELIspot assay was essentially done as described (Lalvani et al.). Briefly, Multi Screen 96-well filtration plates MAIP S4510 (Millipore, Bedford, Mass.) were coated with 10 .mu.g/ml (0.75 .mu.g/well) anti-human IFN-g monoclonal antibody (Mab) B140 (Bender Med Systems, Vienna, Austria) over night at 4.degree. C. Plates were washed 2 times with PBS (Invitrogen Life Technologies) and blocked with ELIspot medium (RPMI 1640 supplemented with 1 mM sodium pyruvate, 2 mM L-glutamine, 0.1 mM non-essential amino acids, 50 .mu.M 2-mercaptoethanol (all from Invitrogen Life Technologies) and 10% human serum type AB (PAA, Linz, Austria). Cryo-preserved PBMC were thawed quickly in a 37.degree. C. water bath, washed 1.times. with ELISPOT medium and incubated overnight (37.degree. C., 5% CO.sub.2). The next day cells were plated at 200,000 PBMC/well and co-cultivated with either individual peptides (10 .mu.g/ml) or peptide pools (each peptide at a final concentration of 5 .mu.g/ml) for 20 hrs. After removing cells and washing 6 times with wash buffer (PBS; 0.1% Tween 20 from SIGMA), 100 .mu.l of a 1:10000 dilution (0.015 .mu.g/well) of the biotinylated anti-human IFN-.gamma. MAb B308-BT2 (Bender Med Systems), was added for an incubation of 2 hrs at 37.degree. C. or alternatively for over night at 4.degree. C. After washing, Streptavidin-alkaline phosphatase (DAKO, Glostrup, Denmark) was added at 1.2 .mu.g/ml for 1 hr at 37.degree. C. The assay was developed by addition of 100 .mu.l/well BCIP/NBT alkaline phosphatase substrate (SIGMA).

In Vitro Priming of Human PBMCs

[0116] Human PBMCs are repeatedly stimulated with antigen (peptide or peptide mixture) in the presence of IL-2 and IL-7. This leads to the selective oligoclonal expansion of antigen-specific T cells. Responses against individual epitopes can be assessed for instance by IFN-.gamma. ELIspot assays. Freshly thawed PBMCs were cultured in 6 well plates (2-4.times.10.sup.6/mL viable cells) in RPMI-1640 (GibcoBRL), 1% non-essential amino acids (GibcoBRL, cat# 11140-035), 1% Penicillin (10,000 U/ml)-Streptomycin (10,000 .mu.g/ml) (GibcoBRL, cat#15140-122), 1% L-Glutamine (GibcoBRL), 0.1% beta-mercapto-ethanol (GibcoBRL), 1% Na-pyruvate (GibcoBRL), plus 10% Human AB serum (PAA, Linz, Austria). Peptides (10 .mu.M each) were added to each well. rhIL-7 (Strathmann Biotech) was added at 10 ng/mL final concentration. 20-30 U/mL rhIL-2 (Strathmann Biotech) were added on day 4. On day 10, all cells were removed from plates, washed once in media (as above), and counted. For the next cycle of in vitro priming, viable cells were co-cultivated with autologous gamma irradiated (1.2 gray/min, for 20 minutes) PBMC as feeders (plated at 100,000 per well) and peptides, rh-IL-2 as described above. ELIspot was done as described above, except that 200,000 responder cells (pre-stimulated for 2 rounds of in vitro priming) were used together with 60,000 autologous irradiated responder cells.

Example I

Rapid Identification of Promiscuous HLA-Binding Peptides from HCV by Measuring Peptide Pools Arrayed in Matrix Format

[0117] To span conserved regions within the HCV polyprotein more than 640 peptides were synthesized (Table 1). For rapid identification of HLA ligands and novel T-cell epitopes, 40 peptide pools each containing 20 single peptides were prepared. The pools were constructed in a way that each peptide was present in 2 pools (matrix format). This allows identification of reactive peptides at the crossover points of row- and column mixtures (FIG. 1 HCV peptide matrix).

TABLE-US-00001 TABLE 1 Synthetic peptides derived from conserved regions of HCV PEP- PEP- PEP- PEP- TIDE SEQ TIDE SEQ TIDE SEQ TIDE SEQ ID ID PEPTIDE ID ID PEPTIDE ID ID PEPTIDE ID ID PEPTIDE A1 203 MSTNPKPQRKTKRNT A79 360 HRSRNVGKVIDTLTC A157 517 CTVNYTIFKIRMYVG A235 674 ADGGCSGGAYDIIIC A2 204 STNPKPQRKTKRNTN A80 361 RSRNVGKVIDTLTCG A158 518 TVNYTIFKIRMYVGG A236 675 DGGCSGGAYDIIICD A3 205 TNPKPQRKTKRNTNR A81 362 SRNVGKVIDTLTCGF A159 519 VNYTIFKIRMYVGGV A237 676 GGCSGGAYDIIICDE A4 206 NPKPQRKTKRNTNRR A82 363 RNVGKVIDTLTCGFA A160 520 NYTIFKIRMYVGGVE A238 677 GCSGGAYDIIICDEC A5 207 PKPQRKTKRNTNRRP A83 364 NVGKVIDTLTCGFAD A161 521 YTIFKIRMYVGGVEH A239 678 CSGGAYDIIICDECH A6 208 KPQRKTKRNTNRRPQ A84 365 VGKVIDTLTCGFADL A162 522 TIFKIRMYVGGVEHR A240 679 SGGAYDIIICDECHS A7 209 PQRKTKRNTNRRPQD A85 366 TLTCGFADLMGYIPV A163 523 IFKIRMYVGGVEHRL A241 680 TTILGIGTVLDQAET A8 210 QRKTKRNTNRRPQDV A86 367 LTCGFADLMGYIPVV A164 524 LPALSTGLIHLHQNI A242 681 TILGIGTVLDQAETA A9 211 RKTKRNTNRRPQDVK A87 368 TCGFADLMGYIPVVG A165 525 PALSTGLIHLEQNIV A243 682 ILGIGTVLDQAETAG A10 212 KTKRNTNRRPQDVKF A88 369 CGFADLMGYIPVVGA A166 526 ALSTGLIHLHQNIVD A244 683 LGIGTVLDQAETAGA A11 213 TKRNTNRRPQDVKFP A89 370 GFADLMGYIPVVGAP A167 527 LSTGLIHLHQNIVDV A245 684 GIGTVLDQAETAGAR A12 214 KRNTNRRPQDVKFPG A90 371 FADLMGYIPVVGAPL A168 528 STGLIHLHQNIVDVQ A246 685 IGTVLDQAETAGARL A13 215 RNTNRRPQDVKFPGG A91 372 ADLMGYIPVVGAPLG A169 529 TGLIHLHQNIVDVQY A247 686 GTVLDQAETAGARLV A14 216 NTNRRPQDVKFPGGG A92 373 DLMGYIPVVGAPLGG A170 530 GLIHLHQNIVDVQYL A248 687 TVLDQAETAGARLVV A15 217 TNRRPQDVKFPGGGQ A93 374 ARALAHGVRVLEDGV A171 531 LIHLHQNIVDVQYLY A249 688 VLDQAETAGARLVVL A16 218 NRRPQDVKFPGGGQI A94 375 RALAHGVRVLEDGVN A172 532 IHLHQNIVDVQYLYG A250 689 LDQAETAGARLVVLA A17 219 RRPQDVKFPGGGQIV A95 376 ALAHGVRVLEDGVNY A173 533 LPALSTGLLHLHQNI A251 690 DQAETAGARLVVLAT A18 220 RPQDVKFPGGGQIVG A96 377 LAHGVRVLEDGVNYA A174 534 PALSTGLLHLHQNIV A252 691 QAETAGARLVVLATA A19 221 PQDVKFPGGGQIVGG A97 378 AHGVRVLEDGVNYAT A175 535 ALSTGLLHLHQNIVD A253 692 AETAGARLVVLATAT A20 222 QDVKFPGGGQIVGGV A98 379 HGVRVLEDGVNYATG A176 536 LSTGLLHLHQNIVDV A254 693 ETAGARLVVLATATP A21 223 DVKFPGGGQIVGGVY A99 380 GVRVLEDGVNYATGN A177 537 STGLLHLHQNIVDVQ A255 694 TAGARLVVLATATPP A22 224 VKFPGGGQIVGGVYL A100 381 VRVLEDGVNYATGNL A178 538 TGLLHLHQNIVDVQY A256 695 AGARLVVLATATPPG A23 225 KFPGGGQIVGGVYLL A101 382 RVLEDGVNYATGNLP A179 539 GLLHLHQNIVDVQYM A257 696 GARLVVLATATPPGS A24 226 FPGGGQIVGGVYLLP A102 383 VLEDGVNYATGNLPG A180 540 LLHLHQNIVDVQYMY A258 697 ARLVVLATATPPGSV A25 227 PGGGQIVGGVYLLPR A103 384 LEDGGVNYATGNLPGC A151 541 LHLHQNIVDVQYMYG A259 698 RLVVLATATPPGSVT A26 228 GGGQIVGGVYLLPRR A104 385 EDGVNYATGNLPGCS A182 542 HLHAPTGSGKSTKVP A260 699 TSILGIGTVLDQAET A27 229 GGQIVGGVYLLPRRG A105 386 DGVNYATGNLPGCSF A183 543 LHAPTGSGKSTKVPA A261 700 SILGIGTVLDQAETA A28 230 GQIVGGVYLLPRRGP A106 387 GVNYATGNLPGCSFS A184 544 HAPTGSGKSTKVPAA A262 701 LGIGTVLDQAETAGV A29 231 QIVGGVYLLPRRGPR A107 388 VNYATGNLPGCSFSI A185 545 APTGSGKSTKVPAAY A263 702 GIGTVLDQAETAGVR A30 232 IVGGVYLLPRRGPRL A108 389 NYATGNLPGCSFSIF A186 546 PTGSGKSTKVPAAYA A264 703 IGTVLDQAETAGVRL A31 233 VGGVYLLPRRGPRLG A109 390 YATGNLPGCSFSIFL A187 547 TGSGKSTKVPAAYAA A265 704 GTVLDQAETAGVRLT A32 234 GGVYLLPRRGPRLGV A110 391 ATGNLPGCSFSIFLL A188 548 GSGKSTKVPAAYAAQ A266 705 TVLDQAETAGVRLTV A33 235 GVYLLPRRGPRLGVR A111 392 TGNLPGCSFSIFLLA A189 549 SGKSTKVPAAYAAQG A267 706 VLDQAETAGVRLTVL A34 236 VYLLPRRGPRLGVRA A112 393 GNLPGCSFSIFLLAL A190 550 GKSTKVPAAYAAQGY A268 707 LDQAETAGVRLTVLA A35 237 YLPRRGPRLGVRAT A113 394 NLPGCSFSIFLLALL A191 551 KSTKVPAAYAAQGYK A269 708 DQAETAGVRLTVLAT A36 238 LLPRRGPRLGVRATR A114 395 LPGCSFSIFLLALLS A192 552 STKVPAAYAAQGYKV A270 709 QAETAGVRLTVLATA A37 239 LPRRGPRLGVRATRK A115 396 PGCSFSIFLLALLSC A193 553 TKVPAAYAAQGYKVL A271 710 AETAGVRLTVLATAT A38 240 PRRGPRLGVRATRKT A116 397 IQLINTNGSWHINRT A194 554 KVPAAYAAQGYKVLV A272 711 ETAGVRLTVLATATP A39 241 RRGPRLGVRATRKTS A117 398 QLINTNGSWEINRTA A195 555 VPAAYAAQGYKVLVL A273 712 TAGVRLTVLATATPP A40 242 RGPRLGVRATRKTSE A118 399 LINTNGSWHINRTAL A196 556 PAAYAAQGYKVLVLN A274 713 AGVRLTVLATATPPG A41 243 GPRLGVRATRKTSER A119 400 INTNGSWINRTALN A197 557 AAYAAQGYKVLVLNP A275 714 GVRLTVLATATPPGS A42 244 PRLGVRATRKTSERS A120 401 NTNGSWHINRTALNC A198 558 AYAAQGYKVLVLNPS A276 715 VRLTVLATATPPGSV A43 245 RLCVRATRKTSERSQ A121 402 TNGSWHINRTALNCN A199 559 YAAQGYKVLVLNPSV B5 716 SGMFDSSVLCECYDA A44 246 LGVRATRKTSERSQP A122 403 NGSWHINRTALNCND A200 560 AAQGYKVLVLNPSVA B6 717 GMEDSSVLCECYDAG A45 247 GVRATRKTSERSQPR A123 404 GSWHINRTALNCNDS A201 561 AQGYKVLVLNPSVAA B7 718 MFDSSVLCECYDAGC A46 248 VRATRKTSERSQPRC A124 405 SWHINRTALNCNDSL A202 S62 QCYKVLVLNPSVAAT B8 719 FDSSVLCECDAGCA A47 249 RATRKTSERSQPRGR A125 406 IQLVNTNGSWHINRT A203 563 GYKVLVLNPSVAATL B9 720 DSSVLCECYDAGCAW A48 250 ATRKTSERSQPRGRR A126 407 QLVNTNGSWHINRTA A204 564 YKVLVLNPSVAATLG B10 721 SSVLCECYDAGCAWY A49 251 TRKTSERSQPRGRRQ A127 408 LVNTNGSWHINRTAL A205 565 KVLVLNPSVAATLGF B11 722 SVLCECYDAGCAWYE A50 252 RKTSERSQPRGRRQP A128 409 VNTNGSWHINRTALN A206 566 VLVLNPSVAATLGFG B12 723 VLCECYDAGCAWYEL A51 253 KTSERSQPRGRRQPI A129 410 VDYPYRLWHYPCTVN A207 567 LVLNPSVAATLGFGA B13 724 LCECYDAGCAWYELT A52 254 TSERSQPRGRRQPIP A130 411 DYPYRLWHYPCTVNF A208 568 VLNPSVAATLGFGAY B14 725 CECYDAGCAWYELTP A53 255 SERSQPRGRRQPIPK A131 412 YPYRLWHYPCTVNFT A209 569 YLHAPTGSGKSTKVP B15 726 ECYDAGCAWYELTA A54 256 DPRRRSRNLGKVIDT A132 413 PYRLWHYPCTVNFTI A210 570 LHAPTGSGKSTKVPV B16 727 CYDAGCAWYELTPAE A55 257 PRRRSRNLGKVIDTL A133 414 YRLWHYPCTVNFTIF A211 571 HAPTGSGKSTKVPVA B17 728 YDAGCAWYELTPAET A56 258 RRRSRNLGKVIDTLT A134 415 RLWHYPCTVNFTIFK A212 572 APTGSGKSTKVPVAY B18 729 DAGCAWYELTPAETT A57 259 RRSRNLGKVIDTLTC A135 416 LWHYPCTVNFTIFKV A213 573 PTGSGKSTKVPVAYA B19 730 AGCAWYELTPAETTV A58 260 RSRNLGKVIDTLTCG A136 417 WHYPCTVNFTIFKVR A214 574 TGSGKSTKVPVAYAA B20 731 GCAWYELTPAETTVR A59 261 SRNLGKVIDTLTCGF A137 418 HYPCTVNFTIFKVRM A215 575 GSGKSTKVPVAYAAQ B21 732 CAWYELTPAETTVRL A60 262 RNLGKVIDTLTCGFA A138 419 YPCTVNFTIFKVRMY A216 576 SGKSTKVPVAYAAQG B22 733 AWYELTPAETTVRLR A61 263 NLGKVIDTLTCGFAD A139 420 PCTVNFTIFKVRMYV A217 577 GKSTKVPVAYAAQGY B23 734 WYELTPAETTVRL.about.A A62 264 LGKVIDTLTCGFADL A140 421 CTVNFTIFKVRMYVG A218 578 KSTKVPVAYAAQGYK B24 735 YELTPAETTVRLRAY A63 265 GKVIDTLTCGFADLM A141 422 TVNFTIFKVRMYVGG A219 579 STKVPVAYAAQGTKV B25 736 DAGCAWYELTPAETS A64 266 KVIDTLTCGFADLMG A142 423 VNFTIFKVRMYVGGV A220 580 TKVPVAYAAQGYKVL B26 737 AGCAWYELTPAETSV A65 267 VIDTLTCGFADLMGY A143 424 NFTIFKVRMYVGGVE A221 581 KVPVAYAAQGYKVLV B27 738 GCAWYELTPAETSVR A66 268 IDTLTCGFADLMGYI A144 425 FTIFKVRMYVGGVEH A222 582 VPVAYAAQGYKVLVL B28 739 CAWYELTPAETSVRL A67 269 DTLTCGFADLMGYIP A145 426 TIFKVRMYVGGVEHR A223 583 PVAYAAQGYKVLVLN B29 740 AWYELTPAETSVRLR A68 270 TLTCGFADLMGYIPL A146 427 IFKVRMYVGGVEHRL A224 584 VAYAAQGYKVLVLNP B30 741 WYELTPAETSVRLPA A69 271 LTCGFADLMGYIPLV A147 428 DYPYRLWHYPCTVNY A225 585 ITSTYGKFLADGGC B31 742 GMFDSVVLCECYDAG A70 272 TCGFADLMGYIPLVG A148 429 YPYRLWHYPCTVNYT A226 586 TYSTYGKFLADGGCS B32 743 SGMFDSVVLCECYDA A71 273 CGFADLMGYIPLVGA A149 430 PYRLWHYPCTVNYTI A227 587 YSTYGKFLADGGCSG B33 744 GMFDSVVLCECYDAG A72 274 GFADLMGYIPLVGAP A150 431 YRLWHYPCTVNYTIF A228 588 STYGKFLADGGCSGG B34 745 MFDSVVLCECYDAGA A73 275 FADLMGYIPLVGAPL A151 432 RLWHYPCTVNYTIFK A229 589 TYGKFLADGGCSGGA B35 746 FDSVVLCECYDAGAA A74 276 ADLMGYIPLVGAPLG A152 433 LWHYPCTVNYTIFKI A230 590 YGKFLADGGCSGGAY B36 747 DSVVLCECYDAGAAW A75 277 DLMGYIPLVGAPLGG A153 434 WHYPCTVNYTIFKIR A231 591 GKFLADGGCSGGAYD B37 748 SVVLCECYDAGAAWY A76 278 DPRHRSRNVGKVIDT A154 435 HYPCTVNYTIFKIRM A232 592 KFLADGGCSGGAYDI B38 749 VVLCECYDAGAAWYE A77 279 PRHRSRNVGKVIDTL A155 436 YPCTVNYTIFKIRMY A233 593 FLADGGCSGGAYDII B39 750 VLCECYDAGAAWYEL A78 280 RHRSRNVGKIDTLT A156 437 PCTVNYTIFKIRMYV A234 594 LADGGCSGGAYDIII B40 751 LCECYDAGAAWYELT B41 281 CECYDAGAAWYELTP B120 438 AGISGALVAFKIMSG C75 595 FPDLGVRVCEKMALY C154 752 DCTMLVNGDDLVVIC B42 282 ECYDAGAAWYELTPA B121 439 GISGALVAFKIMSGE C76 596 PDLGVRVCEKMALYD C155 753 DPTMLVCGDDLVVIC B43 283 CYDAGAAWYELTPAE B122 440 VNLLPAILSPGALVV C77 597 DLGVRVCEKMALYDV

C156 754 DPTMLVNGDDLWIC B44 284 YDAGAAWYELTPAET B123 441 NLLPAILSPGALWG C78 598 KGGKKAARLIVYPDL C157 755 LWARMILMTHFFSIL B45 285 DAGAAWYELTPAETT B124 442 LLPAILSPGALVVGV C79 599 GGKKAARLIVYPDLG C158 756 LWVRMVLMTHFFSIL B46 286 AGAAWYELTPAETTV C1 443 LPAILSPGALVVGVT C80 600 GKKAARLIVYPDLGV C159 757 DLPQIIEELHGLSAF B47 287 GAAWYELTIPAETTV C2 444 PAILSPGALVVGVTC C81 601 KKAARLIVYPDLGVR C160 758 DLPQIIQRLHGLSAF B48 288 AAWYELTPAETTVRL C3 445 AILSPGALVVGVVCA C82 602 KAARLIVYPDLGVEV C161 759 AVRTKLKLTPIPAAS B49 289 DAGAAWYELTPAETS C4 446 ILSPGALVVGVVCAA C83 603 AARLIVYPDLGVEVC C162 760 AVRTKLKLTPLPAAS B50 290 AGAAWYELTPAETSV C5 447 LSPGALVVGVVCAAI C84 604 ARLIVYPDLGVRVCE C163 761 SGGDIYESLSRARPR B51 291 GAAWYELTPAETSVR C6 448 SPGALVVGVVCAAIL C85 605 RLIVYPDLGVRVCEK C164 762 SGGDIYHSVSRARPR B52 292 AAWYELTPAETSVRL C7 449 PGALVVGVVCAAILR C86 606 LIVYPDLGVRVCEKM C165 763 WGENETDVLLLNNTR B53 293 FWAKHMWNFISGIQY C8 450 GALVVGVVCAAILRR C87 607 IVPDLGVRVCEKMA C166 764 GENETDVLLLNNTRP B54 294 WAKHMWNFISGIQYL C9 451 ALVVGVVCAAILRRE C88 608 VYPDLGVEVCEKMAL C167 765 WFGCTWMNSTGFTKT B55 295 AKHMWNFISGIQYLA C10 452 LVVGWCAAILREEV C89 609 YPDLGVRVCEKMALY C168 766 FGCTWMNSTGFTKTC B56 296 KHMENFISGIQYLAG C11 453 VVGVVCAAILEEHVG C90 610 AQPGYPWPLYGNEGL C169 767 GCTWMNSTGFTKTCG B57 297 HMWNFISGIQYLAGL C12 454 VGVVCAAILRRHVGP C91 611 GQPGYPWPLYGNEGL C170 768 GLPVSARRGREILLG B58 298 MWNFISGIQYLAGLS C13 455 GVVCAAILREHVGPG C92 612 AFCSAMYVGDLCGSV C171 769 LPVSARRGREILLGP B59 299 WNFISGIQYLAGLST C14 456 VVCAAILRRHVGPGE C93 613 AFCSALYVGDLCGSV C172 770 PVSARRGREILLGPA B60 300 NFISGIQYLAGLSTL C15 457 VCAAILRRHVGPGEG C94 614 ETVQDCNCSIYPGHV C173 771 VSARRGEEILLGPAD B61 301 FISGIQYLAGLSTLP C16 458 CAAILRRHVGPGEGA C95 615 EFVQDCNCSIYPGHV C174 772 GLPVSALEGREILLG B62 302 ISGIQYLAGLSTLPG C17 459 AAILRRHVGPGEGAV C96 616 GVLAGLAYYSMVGNW C175 773 LPVSALRGREILLGP B63 303 SGIQYLAGLSTLPGN C18 460 AILRRHVGPGEGAVQ C97 617 GVLFGLAYFSMVGNW C176 774 PVSALRGREILLGPA B64 304 GIQYLAGLSTLPGNP C19 461 ILRRHVGPGEGAVQW C98 618 DQRPYCWHYAPRPCG C177 775 VSALRGREILLGPAD B65 305 IQYLAGLSTLPGNPA C20 462 LRRHVGPGEGAVQWM C99 619 DQRPYCWYPPRPCG C178 776 PDREVLYREFDEMEE B66 306 QYLAGLSTLPGNPAI C21 463 RRHVGPGEGAVQWMN C100 620 TCPTDCFRKHPEATY C179 777 DREVLYREFDEMEEC B67 307 YLAGLSTLPGNPAIA C22 464 RHVGPGEGAVQWMNR C101 621 YTKCGSGPWLTPRCL C180 778 REVLYREFDEMEECA B68 308 LAGLSTLPGNPAIAS C23 465 HVGPGEGAVQWMNRL C102 622 LNAACNWTRGERCDL C181 779 EVLYREFDEMEECAS B69 309 AGLSTLPGNPAIASI C24 466 VGPGEGAVQWMNRLI C103 623 LNAACNFTRGERCDL C182 780 VLYREFDEMEECASS B70 310 GLSTLPGNPAIASLM C25 467 GPGEGAVQWMNRLIA C104 624 IAQAEAALENLVVLN C183 781 LYREFDEMEECASHL B71 311 LSTLPGNPAIASLMA C26 468 PGEGAVQWMNRLIAF C105 625 IAQAEAALEKLVVLH C184 782 YYLTRDPTTPLARAA B72 312 STLPGNPAIASLMAF C27 469 GEGAVQWMNRLIAFA C106 626 TRVPYFVRAQGLIRA C185 783 YLTRDPTTPLARAAW B73 313 QYLAGLSTLPGNPAV C28 470 EGAVQWMNRLIAFAS C107 627 TRVPYFVRAHGLIPA C186 784 LTRDPTTPLARAAWE B74 314 YLAGLSTLPGNPAVA C29 471 GAVQWMNRLIAFASR C108 628 HAGLRDLAVAVEPVV C187 785 TRDPTTPLARAAWET B75 315 LAGLSTLPGNPAVAS C30 472 AVQWMNRLIAFASRG C109 629 AAGLRDLAVAVEPIV C188 786 RDPTTPLARAAWETA B76 316 AGLSTLPGNPAVASM C31 473 VQWMNRLIAFASRNGN C110 630 ITWGADTAACGDIIL C189 787 DPTTPLARAAWETAR B77 317 GLSTLPGNPAVASMM C32 474 QWMNRLIAFASRGNH C111 631 ITWGAETAACGDIIL C190 788 PTTPLARAWETARH B78 318 LSTLPGNPAVASMMA C33 475 WMNRLIAFASRGNHV C112 632 GQGWRLLAPITAYSQ C191 789 YYLTRDPTTPLARAA B79 319 STLPGNPAVASMMAF C34 476 MNRLAFASRGNHVS C113 633 TAYSQQTRGLLGCII C192 790 YLTRDPTTPLARAAW B80 320 GAAVGSIGLGKVLVD C35 477 NRLIAFASRGNHVSP C114 634 TAYSQQTRGLLGCIV C193 791 LTRDPTTPLAPAAWE B81 321 AAVGSIGLGKVLVDI C36 478 RLIAFASRGNHVSPT C115 635 GCIITSLTGRDKNQV C194 792 TRDPTTPLARAAWET B82 322 AVGSIGLGKVLDIL C37 479 LIAFASRGNHVSPTH C116 636 GCIVVSMTGRDKTQV C195 793 RDPTTPLARAAWETV B83 323 VGSIGLGKVLVDILA C38 480 IAFASRGNHVSPTHY C117 637 VNGVCWTVYHGAGSK C196 794 DPTTPLARAAWETVR B84 324 GSIGLGKVLVDILAG C39 481 AFASRGNHVSPTHYV C118 638 KGPITQMYTNVDQDL C197 795 PTTPLARAAWETVRH B85 325 SIGLGKVLVDILAGY C40 482 VNLLPGILSPGALVV C119 639 KGPITQMYSSAEQDL B86 326 IGLGKVLVDILAGYG C41 483 NLLPGILSPGALVVG C120 640 GDSRGSLLSPRPVSY B87 327 GLGKVLVDILAGYGA C42 484 LLPGILSPGALVVGV C121 641 GDSRGALLSPRPVSY B88 328 LGKVLVDILAGYGAG C43 485 LPGILSPGALVVGVI C122 642 SYLKGSSGGPLLCPS B89 329 GKVLVDILAGYGAGV C44 486 PGILSPGALVVGVIC C123 643 SYLKGSSGGPVLCPS B90 330 KVLVDILAGYGAGVA C45 487 GILSPGALVVGVICA C124 644 GHAVGIFRAAVCTRG B91 331 VLVDILAGYGAGVAG C46 488 ILSPGALVVGVICAA C125 645 GVDPNIRTGVRTITT B92 332 LVDILAGYGAGVAGA C47 489 LSPGALVVGVICAAI C126 646 VPHPNIEEVALSNTG B93 333 VDILAGYGAGVAGAL C48 490 SPGALVVGVICAAIL C127 647 TGEIPFYGKAIPIEV B94 334 DILAGYGAGVAGALV C49 491 PGALVVGVICAAILR C128 648 TGEIPFYGKAIPLEV B95 335 ILAGYGAGVAGALVA C50 492 GALVVGVICAAILRR C129 649 PTSGDVVVVATDALM B96 336 LAGYGAGVAGALVAF C51 493 ALVVGVICAAILRRH C130 650 QTVDFSLDPTFTIET B97 337 AGYGAGVAGALVAFK C52 494 LVVGVICAAILRRHV C131 651 TLHGPTPLLYRLGAV B98 338 GYGAGVAGALVAFKI C53 495 VVGVICAAILERHVG C132 652 VQNEVTLTHPITKYI B99 339 YGAGVAGALVAFKIM C54 496 VGVICAAILERHVGP C133 653 LYREFDEMEECASHL B100 340 GAGVAGALVAFKIMS C55 497 GVICAAILRRHVGPG C134 654 TTLLFNILGGWVAAQ B101 341 AGVAGALVAFKIMSG C56 498 VICAAILRRHVGPGE C135 655 TTLLNILGGWLAAQ B102 342 GVAGALVAFKIMSGE C57 499 CAAILRRHVGPGEG C136 656 PSAASAFVGAGIAGA B103 343 GYGAGVAGALVAEKV C58 500 MNRLIAFASRGNHVA C137 657 PSAATGEVVSGLAGA B104 344 YGAGVAGALVAFKVM C59 501 NRLIAFASEGNHVAP C138 658 TPCSGSWLRDVWDWI B105 345 GAGVAGALVAFKVMS C60 502 RLIAFASEGNRVAPT C139 659 VAAEEYVEVTRVGDF B106 346 AGVAGALVAFKVMSG C61 503 LIAFASEGNHVAPTH C140 660 VAAEEYAEVTRHGDF B107 347 GVAGALVAFKVNSGE C62 504 IAFASRGNHVAPTHY C141 661 FFTEVDGVRLHRYAP B108 348 GKVLVDILAGYGAGI C63 505 AFASRGNHVAPTHYV C142 662 FFTELDGVRLHRYAP B109 349 KVLVDILAGYGAGIS C64 506 KGGRKPARLIVFPDL C143 663 FFTWVDGVQIHRYAP B110 350 VLVDILAGYGAGISG C65 507 GGRKPARLIVFPDLG C144 664 FFTWLDGVQIHRYAP B111 351 LVDILAGYGAGISGA C66 508 GRKPARLIVFPDLGV C145 665 YLVGSQLPCEPEPDV B112 352 VDILAGYGAGISGAL C67 509 RKPARLIVFPDLGVR C146 666 YLVGSQLPCDPEPDV B113 353 DILAGYGAGISGALV C68 510 KPARLIVFPDLGVRV C147 667 LPTWARPDYNPPLLE B114 354 ILAGYGAGISGALVA C69 511 PARLIVFPDLGVRVC C148 668 ASLRQKKVTFDRLQV B115 355 LAGYGAGISGALVAF C70 512 ARLIVFPDLGVRVCE C149 669 ASLRAKKVTFDRLQV B116 356 AGYGAGISGALVAFK C71 513 RLIVFPDLGVRVCEK C150 670 HIRSVWKDLLEDTET B117 357 GYGAGISGALVAFKI C72 514 LIVFPDLGVRVCEKM C151 671 IDTTIMAKNEVFCVQ B118 358 YGAGISGALVAFKIM C73 515 IVFPDLGVRVCEKNA C152 672 VMGSSYGFQYSPGQR B119 359 GAGISGALVAFKIMS C74 516 VFPDLGVRVCEKMAL C153 673 DCTMLVCGDDLVVIC Peptide ID SEQ ID (Ipep) NO: 1506 796 MSTNPKPQRKTKRNTNRRPQDVKFFGCGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPI- PK 1526 797 VNLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLIAFASRCNHVSPTHYV 1545 798 IKGGRHLIFCHSKKKCDELA 1546 799 TVPQDAVSRSQRRGRTGRGR 1547 800 YLVAYQATVCARAQAPPPSWD 1551 801 HLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAY 1552 802 YLHAPTCSGKSTKVPVAYAAQGYKVLVLNPSVAATLGFGAY 1553 803 GAAVGSIGLGKVLVDILAGYGAGVAGALVAFKIMSGE 1554 804 GAAVGSIGLGKVLVDILAGYGAGVAGALVAFKVNSGE 1555 805 GAAVGSIGLGKVLVDILAGYGAGISGALVAFKIMSGE 1556 806 FTEAMTRYSAPPGDPP 1557 807 SSMPPLEGEPGDFDL 1558 808 CGYRRCRASGVLTTS 1559 809 PVNSWLGNIIMYAPT 1560 810 PVNSWLGNIIQYAPT 1561 811 SGMFDSSVLCECYDAGCAWYELTPAETTVRLRAY 1562 812 SGMFDSSVLCECYDAGCAWYELTPAETSVRLRAY 1563 813 SGMFDSVVLCECYDAGAAWYELTPAETTVRLRAY 1564 814 SGMFDSVVLCECYDAGAAWYELTPAETSVRLRAY 1565 815 FWAKHMWNFISCIQYLAGLSTLPGNPAIASLMAF 1577 816 GEVQVVSTATQSFLAT 1578 817 GEVQVLSTVTQSFLGT 1579 818 FTDNSSPPAVPQTFQV 1580 819 FSDNSTPPAVPQTYQV 1581 820 NAVAYYRGLDVSVIPT 1587 821 VNLLPGILSPGALVVGVICAAILRRHVGPGEGAVQWMNRLIAFASRGNHVAPTHYV

1588 822 TTILGIGTVLDQAETAGARLVVLATATPPGSVT 1589 823 TSILGIGTVLDQAETAGARLVVLATATPPGSVT 1590 824 TSILGIGTVLDQAETAGVRLTVLATATPPGSVT 1591 825 TTILGIGTVLDQAETAGVRLTVLATATPPGSVT 1592 826 FWAKHMWNFISGIQYLAGLSTLPGNPAVASMMAF 1603 827 VFTGLTHIDAHFLSQTKQ 1604 828 VVCCSMSYTWTGALITPC 1605 829 VVCCSMSYSWTGALITPC 1606 830 VLTSMLTDPSHITAETA 1607 831 VLTSMLTDPSHITAEAA 1613 832 ASSSASQLSAPSLRATCTT 1614 833 LTPPHSARSKFGYGAKDVR 1615 834 LTPPHSADSKFGYGAKDVR 1616 835 LTPPHSAKSKYGYGAKEVR 1617 836 LTPPHSARSKYGYGAKEVR 1618 837 PMGFSYDTRCFDSTVTE 1619 838 PMGFAYDTRCFDSTVTE 1620 839 TGDFDSVIDCNTCVTQ 1621 840 TGDFDSVIDCNVAVTQ 1622 841 NTPGLPVCQDHLEFWE 1623 842 YLVAYQATVCARAXAPPPSWD 1624 843 LEDRDRSELSPLLLSTTEW 1625 844 LEDRDRSQLSPLLHSTTEW 1626 845 ASSSASQLSAPSLKATCTT 1627 846 PEYDLELITSCSSNVSVA 1628 847 VCGPVYCFTPSPVVVGTTDR 1629 848 GWAGWLLSPRGSRPSWGP 1630 849 LLFLLLADARVCACLWM 1631 850 SGHRMAWDMMMNWSPT 1632 851 TGHRMAWDMMMNWSPT 1641 852 ITYSTYGKFLADGGCSGGAYDIIICDECHS 1647 853 ARALAHGVRVLEDGVNYATGNLPGCSFSIFLIALLSC 1648 854 DPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGG 1649 855 DPRHRSRNVGKVIDTLTCGFADLMGYIPVVGAPLGG 1650 856 VDYPYRLWHYPCTVNFTIFKVRMYVGGVEHRL 1651 857 VDYPYRLWHYPCTVNYTIFKIRMYVGGVEHRL 1652 858 XGGRKPARLIVFPDLGVRVCEKMALYDV 1653 859 KGGKKAARLIVYPDLGVRVCEKMALYDV 1654 860 IQLTNTNGSWHTNRTALNCNDSL 1655 861 IQLVNTNGSWHINRTALNCNDSL 1656 862 LPALSTGLIHLHQNIVDVQYLYG

[0118] For epitope capture, each peptide pool was incubated with soluble recombinant HLA-class II molecules and specific binding was assessed by an SDS-stability assay. The results using the HLA molecules DRB1*0401, DRB1*0404 and DRB1*0101 are shown in FIGS. 2 and 3 respectively: 28 peptide pools were found which bind to DRB1*0401 molecules: no. 1, 2, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19, 20 from "row" pools and no. 23, 25, 26, 27, 29, 30, 31, 34, 36, 38, 39 and 40 from "column" pools (FIG. 2). 35 peptide pools out of 40 tested were positive in binding to DRB1*0404 molecules (FIG. 3), while all peptide pools showed binding activity to DRB1*0101 molecules. By finding the intersections of reactive pools in the array, potential individual binders were determined and re-checked for binding affinity individually.

[0119] All individually confirmed peptides are summarized in Table 2. Binding to DRB1*0401 is shown in FIG. 4: 54 individual peptides were identified as ligands of this HLA-type. Often several overlapping 15mers in a row bound to HLA allowing identification of their core binding regions. Peptide differing only by one or two amino acids representing variants (see Table 1) usually bound both to soluble HLA class II molecules. Such "duplicates" were considered to represent the same epitope. Thus, 31 ligands capable to bind to DRB1*0401 were identified, including 11 previously known class II epitopes. From the latter, however, only two (A202-A206 and B60-B68) had been known to be restricted to DR4 (see Table 2). 20 ligands are candidates for novel epitopes. For DRB1*0404, 64 binders designated as 28 potential epitopes were determined, 4 of them belong to already known epitopes (FIG. 5, Table 2). For DRB1*0101, 83 peptides representing 44 potential epitopes were identified (FIG. 6, Table 2). Of those, 7 had been described previously but with different HLA restriction.

[0120] All individually confirmed peptides binding to at least one of the 3 above mentioned HLA types were also tested for affinity to molecules in a peptide-competition assay (FIG. 7, Table 2). Here, 50 ligands were identified. Of those, 7 correspond to already known class II epitopes, but only one was described as DRB1*0701 epitope (A202-A206).

TABLE-US-00002 TABLE 2 HCV derived peptides binding to soluble HLA class II molecules. About 400 15- to 23-mer peptides derived from conserved regions of HCV were analyzed by the Epitope Capture Method using pools of up to 20 peptides arrayed in matrix format (see FIG. 1) and four different HLA class II molecules. Specific binding was confirmed for individual peptides. Known/new SEQ potential ID Binding to DRB1 epitope, HLA ID NO: Peptide Sequences *0101 *0401 *0404 *0701 coverage A120 863 NTNGSWHINRTALNC * nb new DRB1*0101, A122 864 NGSWHINRTALNCND * * * *0404, *0701: 45- A124 865 SWHINRTALNCNDSL * 55% B25 866 DAGCAWYELTPAETS *** * *** new DRB1*0101, B26 867 AGCAWYELTPAETSV *** *** *** nb *0404, *0701: 45- B28 868 CAWYELTPAETSVRL *** ** *** * 55% B30 869 WYELTPAETSVRLRA ** * ** nb B46 870 AGAAWYELTPAETTV *** *** nb new DRB1*0101, B48 871 AAWYELTPAETTVRL *** *** ** *0404, *0701: 45- 55% B84 872 GSIGLGKVLVDILAG * * * new DRB1*0101, B86 873 IGLGKVLVDILAGYA * ** * ** *0404, *0701: 45- B88 874 LGKVLVDILAGYGAG * ** * 55% B92 875 LVDILAGYGAGVAGA * nb C106 876 TRVPYFVRAQGLIRA * * * * new DRB1*0101, *0404, *0701: 45- 55% C113 877 TAYSQQTRGLLGCII *** * new DRB1*0101, C114 878 TAYSQQTRGLLGCIV *** * * * *0404, *0701: 45- 55% 1627 879 PEYDELELITSCSSNVSVA *** *** ** new DRB1*0101, *0404, *0701: 45- 55% 1628 880 VCGPVYCFTPSPVVVGTTDR *** ** * * new DRB1*0101, *0404, *0701: 45- 55% 1629 881 GWAGWLLSPRGSPRPSWGP * * ** * new DRB1*0101, *0404, *0701: 45- 55% 1604 882 VVCCSMSYTWTGALITPC * ** *** new DRB1*0101, *0404, *0701: 45- 55% 1630 883 LLFLLLADARVCACLWM * nb *** new DRB1*0101, *0701: 40-50% C97 884 GVLFGLAYFSMVGNW ** ** nb ** new DRB1*0101, *0701: 40-50% 1547 885 YLVAYQATVCARAQAPPPSWD *** NB ** new DRB1*0101, *0701: 40-50% B94 886 DILAGYGAGVAGALV * nb nb nb new DRB1*0101, B95 887 ILAGYGAGVAGALVA * nb nb *0404, *0701: 40- B96 888 LAGYGAGVAGALVAF ** ** nb * 50% B97 889 AGYGAGVAGALVAFK * nb nb B98 890 GYGAGVAGALVAKFI * nb nb nb A272 891 ETAGVRLTVLATATT * * nb new DRB1*0101, A274 892 AGVRLTVLATATPPG * nb nb *0404, *0701: 40- A276 893 VRLTVLATATPPGSV nb * 50% B120 894 AGISGALVAFKIMSG * nb * *** new DRB1*0101, *0404, *0701:~45 B122 895 VNLLPAILSPGALVV * nb * * new DRB1*0101, *0404, *0701:~45 C108 896 HAGLRDLAVAVEPVV * nb * * new DRB1*0101, *0404 *0701:~45 C134 897 TTLLFNILGGWVAAQ * nb * ** new DRB1*0101, *0404, *0701:~45 C152 898 VMGSSYGFQYSPGQR * nb * * new DRB1*0101, *0404, *0701:~45 1606 899 VLTSMLTDPSHITAETA nb *** ** ** new DRB1*0401, *0404, *0701:~45 1607 900 VLTSMLTDPSHITAEAA nb *** ** * new DRB1*0401, *0404, *0701:~45 1577 901 GEVQVVSTATQSFLAT nb * *** *** new DRB1*0401, *0404, *0701:~45 1578 902 GEVQVLSTVTQSFLGT nb * *** *** new DRB1*0401, *0404, *0701:~45 B50 903 AGAAWYBLTPAETSV *** *** *** new DRB1*0101, B52 904 AAWYELTPAETSVRL *** *** *** nb *0401, *0404:~40 1623 905 YLVAYQATVCARAKAPPPSWD * ** new DRB1*0101, *0401, *0404:~40 C130 906 QTVDFSLDPTFTTET ** *** ** nb new DRB1*0101, *0401, *0404:~40 1603 907 VFTGLTHIDAHFLSQTKQ *** nb nb * new DRB1*0101, *0701: ~-40 C96 908 GVLAGLAYYSMVGNW ** nb nb * new DRB1*0101, *0701: ~-40 C191 909 YYLTRDPTTPLAPAA nb *** nb new DRB1*0401, *0701:~40 A216 910 SGKSTKVPVAYAAQG nb * nb nb new DRB1*0101, A218 911 KSTKVPVAYAAQGYK nb * nb *0401:~35 A220 912 TKVPVAYAAQGYKVL * ** nb A222 913 VPVAYAAQGYKVLVL * nb nb nb A224 914 VAYAAQGYKVLVLNP * nb nb A242 915 TILGIGTVLDQAETA nb nb * new DRB1*0101, A244 916 LGIGTVLDQAETAGA * * nb nb *0401:~35 C92 917 AFCSANYVGDLCGSV * ** nb nb new DRB1*0101, C93 918 AECSALYVGDLCGSV * * nb *0401:~35 A174 919 PALSTGLLHLHQNTV nb * * new DRB1*0404, *0701:~25-30 B32 920 SGMFDSVVLCECYDA * nb *** new DRB1*0101, B34 921 MFDSVVLCECYDAGA * nb *** nb *0404:~20-25 B36 922 DSVVLCECYDAGAAW * nb *** B38 923 VVLCECYDAGAAWYE nb nb * nb B100 924 GAGVAGALVAFKIMS ** nb ** new DRB1*0101, B102 925 GVAGALVAFKIMSGE *** nb *** *0404:~20-25 C135 926 TTLLLNILGGWLAAQ ** nb * new DRB1*0101, *0404:~20-25 C162 927 AVRTKLKLTPLPAAS nb * * nb new DRB1*0401, *0404:~20-25 1618 928 PMGFSYDTRCFDSTVTE nb nb ** new DRB1*0701:~25 1622 929 NTPGLPVCQDHLEFWE nb nb *** new DRB1*0701:~25 1624 930 LEDRDRSELSPLLLSTTEW nb nb * new DRB1*0701:~25 1546 931 TVPQDAVSRSQRRGRTGRGR nb nb nb * new DRB1*0701:~25 1556 932 FTEAMTRYSAPPGDPP nb nb nb * new DRB1*0701:~25 A114 933 LPGCSFSIFLLALLS ** nb nb nb new DRB1*0101:~20 B58 934 MWNFISGTQYLAGLS * nb nb new DRB1*0101:~20 B112 935 VDTLAGYGAGISGAL * new DRB1*0101:~20 B114 936 ILAGYGAGISGALVA *** B116 937 AGYGAGISGALVAFK *** nb nb B118 938 YGAGISGALVAFKIM *** nb B18 939 DAGCAWYELTPAETT *** nb nb new DRB1*0101:~20 B20 940 GCAWYELTPAETTVR *** nb B22 941 AWYELTPAETTVRLR ** nb nb C112 942 GQGWRLLAPTTAYSQ ** nb new DRB1*0101:~~20 C116 943 GCIVVSMTGRDKTQV * nb nb new DRB1*0101:~20 C122 944 SYLKGSSGGPLLCPS * nb nb new DRB1*01O1:~20 C127 945 TGEIPFYGKAIPTEV * nb new DRB1*0101:~20 C144 946 FFTWLDGVQIHRYAP ** nb nb new DRB1*0101:.~20 C159 947 DLPQIIERLHGLSAF * nb nb nb new DRB1*0101:~2 C160 948 DLPQIIQRLHGLSAF * nb C174 949 GLPVSALRGRETLLG * nb nb new DRB1*0101:~20 1558 950 CGYRRCRASGVLTTS *** nb nb new DRB1*0101:~20 1581 951 NAVAYYRGLDVSVIPT ** nb nb nb new DRB1*0101:~20 C95 952 EFVQDCNCSIYPGHV nb ** nb nb new DRB1*0401:~20 C129 953 PTSGDVVVVATDALM nb nb ** new DRB1*0404:~5 C157 954 LWARMILMTHFFSIL nb nb * nb new DRB1*0404:~5 C158 955 LWVRMVLMTHFFSIL nb * A254 956 ETAGARLVVLATATP nb nb * new DRB1*0404:~5 A256 957 AGARLVVLATATPPG nb nb * A258 958 ARLVVLATATPPGSV nb nb ** 1605 959 VVCCSMSYSWTGALITPC nb nb * nb new DRB1*0404:~5 C109 960 AAGLRDLAVAVEPIV nb * new DRB1*0404:~5 C161 961 AVRTKLKLTPIPAAS nb * new DRB1*0404:~5 A60 962 LGKVIDTLTCGFA ** nb nb ** known DR4, DR8, DR15 A61 963 GKVIDTLTCGFAD ** new DR*0101, 0701 A70 964 TCGFADLMGYIPLVG * nb nb known class II A72 965 GFADLMGYIPLVGAP *** * ** DR*0101, 0404, A74 966 DLMGYIPVVGAPLGG *** *** ** 0701 A88 967 CGFADLMGYIPVVGA ** ** * known class II A90 968 FADLMGYIPVVGAPL *** *** DR*0101, 0404, A92 969 DLMGYIPVVGAPLGG *** *** *** 0701 A96 970 LAHGVRVLEDGVNYA nb *** nb known DR11 A98 971 HGVRVLEDGVNYATG nb *** *** ** new DR*0401, A100 972 VRVLEDGVNYATGNL nb *** *** * 0404, 0701 A102 973 VLEDGVNYATGNLPG nb * A104 974 EDGVNYATGNLPGCS nb * nb nb A200 975 AAQGYKVLVLNPSVA nb *** ** known DRB1*0401, A202 976 QGYKVLVLNPSVAAT *** *** *** *** 0701, DR11, DR15 A204 977 YKVLVLNPSVAATLG *** *** *** *** new DR*0101 A206 978 VLVLNPSVAATLGFG *** *** *** *** C30 979 AVQWMNRLIAFASRG * nb known DR11, DQ5, also DR*0101 B60 980 NFISGIQYLAGLSTL ** nb 8 known DR#40401, B62 981 ISGIQYLAGLSTLPG *** *** ** 1101 B64 982 GIQYLAGLSTLPGNP *** *** ** new 0101, 0404, B66 983 QYLAGLSTLPGNPAI * *** ** 0701 B68 984 LAGLSTLPGNPAIAS * *** ** C124 985 GHAVGIFRAAVCTRG ** * nb ** known DR*0101, 0401, 0701 1620 986 TGDFDSVIDCNTCVTQ nb nb * new DR*0404 1621 987 TGDFDSVIDCNVAVTQ * nb nb known DR13, also DR*0101, 0401 1631 988 SGHRMAWDMMMNWSPT nb nb known class II, also DR*0401 1632 989 TGHRMAWDMMMNWSPT nb * known class II,

also DR*0401 *** strong binding ** intermediate binding * weak binding nb no binding Boldface peptide IDs indicates HLAligands with confirmed immunogenicity in HLA-transgenic mice Boldface peptide sequences indicate putative core binding regions based on prediction algorithms as descnbed in the test. .sup.1)immunogenic in DRB1 *0401 transgenic mice.

[0121] Some of the highly promiscuous peptides and/or with computer algorithm (SYFPEITHI (SEQ ID NO:203), TEPITOPE (SEQ ID NO:204))-predicted affinities were checked for binding to soluble HLA-DRB1*1101 molecules in a peptide-competition assay as it is described for HLA-DRB1*0701. Several known DR11 epitopes were used as controls and were confirmed to bind HLA-DRB1*1101 molecules in vitro. Among newly identified HLA-DRB1*1101 binders, there are peptides with IDs A120, A122, A141, C114, C134, 1426, 1628, 1629 of high affinity, 5 peptides with IDs C106, C135, 1578, 1547, 1604 of moderate affinity and 4 peptides with IDs B46, B48, B86, B96 of weak affinity ligands.

[0122] In summary eight novel ligands binding at least to HLA-DRB1*0101, *0401, *0404, *0701 and *1101 (Tab. 2: peptide Ids A120, A122, A141, 1604, 1547, 1628, 1629, and Tab. 6: peptide ID 1426); novel 10 ligands binding at least to HLA-DRB1*0101, *0401, *0404 and *0701 (Tab. 2: peptide IDs A120-A124, B25-B30, B46-B48, B84-B92, C106, C113-C114, 1627, 1628, 1629, 1604); 5 novel ligands binding at least to HLA-DRB1*0101, *0401 and *0701, 5 novel ligands binding at least to HLA-DRB1*0101, *0404 and *0701, 4 novel ligands binding at least to HLA-DRB1*0401, *0404 and *0701, 3 novel ligands binding at least to HLA-DRB1*0101, *0401 and *0404, 2 novel ligands binding at least to HLA-DRB1*0101 and *0701, 1 novel ligand binding at least to HLA-DRB1*0401 and *0701, 3 novel ligands binding at least to HLA-DRB1*0101, *0401, 1 novel ligand binding at least to HLA-DRB1*0404 and *0701, 4 novel ligand binding at least to HLA-DRB1*0101 and *0404, 5 novel ligands binding at least to HLA-DRB1*0701, 13 novel ligands binding at least to HLA-DRB1*0101, 1 novel ligand binding at least to HLA-DRB1*0401, and 6 novel ligands binding at least to HLA-DRB1*0404.

[0123] Moreover, 12 known HLA class II epitopes were confirmed, in several cases binding to alleles not reported yet was demonstrated (Tab. 2, last group).

[0124] Having established physical binding too HLA class II it is straightforward to verify immunogenicity for a given ligand: for instance peptide IDs A120-A124, B46-B48, 1627, 1604, 1630, 1547, 1623, B112-118, 1558, all binding to one or more HLA class II alleles were also shown to be immunogenic in HLA-DRB1*0401 transgenic mice (see Example II).

[0125] To determine the optimal epitope within a longer polypeptide, mice can be vaccinated with a longer polypeptide incorporating the candidate epitope sequences. Generation of specific CD4+ T cell responses against naturally processed and presented epitopes can then be assayed by re-stimulation of murine splenocytes or lymph node cells with overlapping 15-mers and IFN-gamma ELIspot. Final confirmation/validation of the newly identified HLA-ligands can be achieved by testing these peptides with T-cells from humans. Ideally, these comprise therapy responders or subjects spontaneously recovered from infection.

Example II

Immunogenicity of HCV-Derived Peptides in HLA-Transgenic Mice

[0126] Synthetic HCV-derived peptides (from conserved regions) were investigated for immunogenicity in HLA-transgenic mice: 36 of 68 peptides tested were found to induce peptide-specific IFN-gamma-producing cells in vaccination experiments. As summarized in Table 3, some peptides were either immunogenic (+, less than 100 peptide-specific cells among a million splenocytes) or even strongly immunogenic (++, more than 100 peptide-specific cells among a million splenocytes) in DR4- and/or A*0201-transgenic mice.

TABLE-US-00003 TABLE 3 DRB1* SEQ ID Ipep 0401 A*0201 B*0702 NO Sequence 1506 + 990 MSTNPKPQRKTKTNRRPQD VKFPGGGQIVGGVYLLPRR GPRLGVATRKTSERSQPRG RRQPIPK 1526 + + + 991 VNLLPAILSPGALVVGVVC AAILRRHVGPGEGAVQWMN RLIAFASRGNHVSPTHYV 1545 + 992 IKGGRHLIFCHSKKKCDEL A 1547 ++ +++ 993 YLVAYQATVCARAQAPPPS WD 1552 + + 994 YLHAPTGSGKSTKVPVAYA AQGYKVLVLNPSVAATLGF GAY 1553 + + 995 GAAVGSIGLGKVLVDILAG YGAGVAGALVAFKIMSGE 1555 + + + 996 GAAVGSIGLGKVLVDILAG YGAGISGALVAFKIMSGE 1558 ++ + ++ 997 GGYRRCRASGVLTTS 1559 + ++ 998 PVNSWLGNIIMYAPT 1560 + ++ 999 PVNSWLGNIIQYAPT 1562 + 1000 SGMFDSSVLCECYDAGCAW YELTPAETSVRLRAY 1563 + + 1001 SGMFDSVVLCECYDAGAAW YELTPAETTVRLRAY 1565 ++ ++ + 1002 FWAKHMWNFISGIQYLAGL STLPGNPAIASLMAF 1577 + + 1003 GEVQVVSTATQSFLAT 1578 + 1004 GEVQVLSTVTQSFLGT 1580 + 1005 FSDNSTPPAVPQTYQV 1587 + + 1006 VNLLPGILSPGALVVGVIC AAILRRHVGPGEGAVQWMN RLTAFASRGNHVAPTHYV 1592 ++ ++ + 1007 FWAKHMWNFISGIQYLACL STLPGNPAVASMMAF 1604 ++ ++ ++ 1008 VVCCSMSYTWTGALITPC 1605 + + + 1009 VVCCSMSYSWTGALITPC 1615 + 1010 LTPPHSAKSKFGYGAKDVR 1616 + 1011 LTPPHSAKSKYGYGAKEVR 1617 + 1012 LTPPHSARSKYGYGAKEVR 1621 + + + 1013 TGDFDSVIDCNVAVTQ 1623 + + + 1014 YLVAYQATVCARAKAPPPS WD 1624 + 1015 LEDRDRSELSPLLLSTTEW 1625 + 1016 LEDRDRSQLSPLLHSTTEW 1627 + + ++ 1017 PEYDLELITSCSSNVSVA 1628 ++ 1018 VCGPVYCFTPSPVVVGTTDR 1630 ++ ++ 1019 LLFLLLADARVCACLWM 1631 + + 1020 SGHRMAWDMMMNWSPT 1632 + 1021 TGHRMAWDMMMNWSPT 1641 + 1022 ITYSTYGKFLADGGCSGGA YDIIICDECHS 1647 + + 1023 ARALAHGVRVLEDGVNYAT GNLPGCSFSIFLLALLSC 1649 + 1024 DPRHRSRNVGKVIDTLTCG FADLMGYIPVVGAPLGG 1650 ++ ++ + 1025 VDYPYRLWHYPCTVNFTIF KVRNYVGGVEHRL 1651 ++ ++ + 1026 VDYPYRLNHYPCTVNYTIF KTRNYVGGVEHRL 1652 ++ + 1027 KGGRKPARLIVFPDLGVRV CEKMALYDV 1653 + 1028 KGGKKAARLIVYPDLGVRV CEKMALYDV 1654 ++ + 1029 IQLINTNGSWHINRTALNC NDSL 1655 ++ + 1030 IQLVNTNGSWHTNRTALNC NDSL 1656 + 1031 LPALSTGLIHLHQNIVDYQ YLYG

[0127] Peptide 1526, 1565, 1631, also shown to be immunogenic in HLA-DRB1*0401 transgenic mice contain known class II epitopes. Peptide IDs 1526, 1553, 1565, 1587, 1623, 1630 also shown to be immunogenic in HLA-A*0201 transgenic mice contain known A2 epitopes.

[0128] For further characterizing the novel epitopes provided herewith, one may define the exact HLA restriction of these epitopes and the minimal epitopes within the sequences recognized by T cells. Both can be done by a variety of well-established approaches known to the one skilled in the art (Current Protocols in Immunology, John Wiley& Sons, Inc.).

[0129] First, publicly available programs can be used to predict T cell epitopes on the basis of binding motifs. These include for instance: http://bimas.dcrt.nih.gov/molbio/hla_bind/ (Parker et al. 1994), http://134.2.96.221/scripts/MHCServer.dll/home.htm (Rammensee at al. 1999), http://mypage.ihost.com/usinet.hamme76/(Sturniolo et al. 1999). The latter prediction algorithm offers the possibility to identify promiscuous T helper-epitopes, i.e. peptides that bind to several HLA class II molecules. These predictions can be verified by testing of binding of the peptide to the respective HLA.

[0130] A way of quickly discerning whether the response towards a peptide is class I or class II restricted is to repeat the ELIspot assay with pure CD4+ or CD8+ T cell effector populations. This can for instance be achieved by isolation of the respective subset by means of magnetic cell sorting. Pure CD8+ T cells can also be tested in ELIspot assays together with artificial antigen-presenting-cells, expressing only one HLA molecule of interest. One example are HLA-A*0201 positive T2 cells (174CEM.T2, Nijman et al., 1993). Alternatively, one can use ELIspot assays with whole PBMCs in the presence of monoclonal antibodies specifically blocking either the CD4+ or CD8+ T cell sub-population. Exact HLA restriction can be determined in a similar way, using blocking monoclonal antibodies specific for a certain allele. For example the response against an HLA-A24 restricted epitope can be specifically blocked by addition of an HLA-A24 specific monoclonal antibody.

[0131] For definition of the minimal epitopes within the peptide sequences recognized by T cells, one can test overlapping and truncated peptides (e.g. 8-, 9-, 10-mers) with splenocytes from immunized transgenic mice or T-cells from humans recognizing the respective epitope.

Example III

HLA Restriction of Immunogenic HCV-Derived Peptides Investigated in Transgenic Mice

[0132] Groups of 5 mice (HLA-A*0201-, HLA-DRB1*0401- and HLA-B*0702 transgenic mice, male, 8-14 weeks of age) were injected subcutaneous into the hind footpads with 100 .mu.g of peptide+IC31 per mouse (50 .mu.g per footpad). (PCT/EP01/12041, WO 02/32451 A1 and PCT/EP01/06433, WO 01/93905 A1; IC31 is a combination of the immunizer disclosed in WO 01/93905 and WO 02/32451).

[0133] 6 days after vaccination single cell suspension of pooled spleens were prepared and additionally pure fractions of CD8+ in the case of A2 and B7 .mu.g mice (CD8+ fraction for B7 mice containing 97% of CD8 and 1.5% of CD4 cells and for A2tg mice 83% of CD8 and 8% of CD4 cells) and CD4+ for DR4tg mice (CD4+ fraction for DR4tg mice containing 98% of CD4 cells and 0.2% of CD8 cells) were separated from the spleen cell suspension using MACS separating kit (Miltenyi, Germany). All cells (not separated cells, positive and corresponding negative fractions) were re-stimulated ex vivo with relevant peptide (for instance Ipep1604) and irrelevant peptides as negative control (known HLA-DRB1*0401 CMV-derived epitope Ipep 1505, HLA-B*0702 HIV-derived epitope Ipep 1787, or HLA-A*0201 tyrosinase-derived epitope Ipep1124) to detect INF-.gamma. producing cells in ELISpot assay.

[0134] As an example shown in FIG. 8-10 the Ipep1604 (VVCCSMSYTWTGALITPC (SEQ ID NO:30), in combination with immunizer IC31) was able to induce high numbers of specific INF-.gamma. producing T cells in all three transgenic class I and II mouse strains. This was shown not only with whole spleen derived cells but also with enriched fractions of CD8+ cells correspondingly for A2 and B7 and CD4+ cells for DR4tg mice. Similar, albeit weaker responses were seen with Ipep1605 (VVCCSMSYSWTGALITPC (SEQ ID NO:126)), a sequence variant with a serine instead of a threonine.

[0135] Thus, Ipep1604 contains class I epitopes for HLA-A*0201 and HLA-B*0702 and a class II epitope for HLA-DRB1*0401 molecules.

[0136] As shown in Tables 2 and 6, Ipep 1604 binds to class II molecules in a promiscuous manner. Thus, it contains further epitopes, at least for HLA-DRB1*0101, DRB1*0404, DRB1*0701 and DRB1*1101.

[0137] Other peptides were analysed in a similar way:

Ipeps 1605, 1623, 1547, 1558, 1559, 1560, 1565, 1592, 1650, 1654 and 1655 were confirmed to contain human HLA-DRB1*0401 epitopes. Again, for most of these epitopes binding is not limited to HLA-DRB1*0401 as shown in Tables 2 and 6.

[0138] Ipeps 1565, 1605 and 1650 were confirmed to contain human HLA-A*0201 epitopes.

[0139] Ipeps 1506, 1587 were confirmed to contain human HLA-B*0702 epitopes.

[0140] Ipep 1843 with sequence LPRRGPRL (SEQ ID NO:1046) was shown to be the HLA-B*0702 minimal epitope contained in 1506:

[0141] FIG. 10 shows mouse IFN-gamma ELIspot with splenocytes or separated CD8+ or CD4+ cells from HLA-A*0702 transgenic mice vaccinated with Ipep1506+IC31 or Ipep1835+IC31.

[0142] FIGS. 10 A) and B) shows that after a single vaccination with either Ipep 1506+IC31 or Ipep1835+IC31, upon restimulation with overlapping 15mers, the 15mers A30 to A37 (see Tab.1) react. The common sequence of these 15mers is LPRRGPRL (SEQ ID NO:1046) (Ipep 1843, see Tab.4).

[0143] FIG. 10 C) confirms these findings: after a single vaccination with either Ipep1506+IC31 or Ipep1835+IC31, significant interferon-gamma induction against Ipep1843 can be detected. In both cases Ipep 1790 an HIV NEF-derived HLA-B*0702 epitope (sequence RPMTYKAAL (SEQ ID NO:1032)) was used as negative control for restimulation.

[0144] Ipep 1838 with sequence SPGALVVGVI (SEQ ID NO:1045) (see Tab.4) was shown to be an HLA-B*0702 minimal epitope contained in 1587: In the case of Ipep1587 a different approach was taken: the sequence of Ipep1587 was inspected for HLA-B*0702 binding motifs and a couple of short peptides were synthesized accordingly. These were tested in a competition-type peptide binding assay using soluble HLA-B*0702 and the FITC-labelled reference peptide LPCVLWPVL (SEQ ID NO:1033), which is a known HLA-B*0702 epitope derived from EBV (Stuber et al., 1995). Peptide Ipep1838 showed .about.30% competition when used in 80-fold molar excess for 48 h at 37.degree. C. Thus it is likely to present the minimal HLA-B*0702 epitope contained in Ipep 1587.

Example IV

Identification and Confirmation of Novel HCV Peptides Reactive in IFN-Gamma ELIspot with Human PBMC from HCV Therapy Responders or Patients with Spontaneous Recovery

[0145] 40 peptide mixtures in matrix format (FIG. 1) containing synthetic peptides derived from conserved regions of HCV (Table 1) were screened in IFN-gamma ELIspot using PBMC from more than 50 individuals who were either responders to interferon/ribavirin standard therapy, or, who had spontaneously cleared HCV (i.e. all subjects were HCV antibody positive, but HCV-RNA negative). PBMC from such individuals are supposed to contain the relevant T-cell populations responsible for clearing HCV. Thus, peptides discovered or confirmed by using these PBMC are likely to represent the structural determinants of immune protection against/clearance of HCV. Based on the results from this primary matrix-screen, a number of peptides were chosen for individual re-testing in IFN-gamma ELIspot using PBMC from selected donors. In addition, several new peptides incorporating sequences from overlapping reactive peptides or avoiding critical residues like cystein were synthesized. These are summarized in Table 4.

TABLE-US-00004 TABLE 4 additional peptides derived from conserved regions of HCV. Peptide sequence Peptide ID (1 amino acid code) SEQ ID NO: 1006 MWNFISGIQYLAGLSTLPGN 1034 1334 HMWNFISGI 1035 1425 NFISGIQYLAGLSTLPGNPA 1036 1426 HMWNFISGIQYLAGLSTLPGNPA 1037 1798 IGLGKVLVDILAGYGAGVAGALVAFK 1038 1799 AAWYELTPAETTVRLR 1039 1800 DYPYRLWHYPCTVNYTIFKI 1040 1836 DYPYRLWHYPCTVNFTIFKI 1041 1801 AYSQQTRGLL 1042 1827 TAYSQQTRGLLG 1043 1829 SMSYTWTGALITP 1044 1838 SPGALVVGVI 1045 1843 LPRRGPRL 1046

[0146] Results of the secondary screening with individual peptides are summarized in Table 5. Altogether .about.20% of subjects (G05, G18, H02, H03, H04, H10, H12, H19, H32, H38) showed a significant IFN-gamma T-cell response against one or more of the peptides. In some cases the observed number of ELIspots was clearly elevated, but not statistically significant above background. In these cases, PBMC (donors H03, H10, H33, H38) were stimulated with the respective peptides in vitro (2 rounds of in vitro priming, see Material & Methods) in order to increase the peptide specific response. Several peptides were confirmed in this way, results are again summarized in Table 5.

[0147] Peptides A3-A7 represent overlapping 15mers spanning the sequence TNPKPQRKTKRNTNRRPQD (SEQ ID NO:1047). Since they all react with PBMC from donor H03, the minimal sequence of the epitope is located within the sequence PQRKTKRNTNR (SEQ ID NO:1048). Prediction algorithms indicate that QRKTKRNTN (SEQ ID NO:1049) and QRKTKRNT (SEQ ID NO:1050) represent ligands of HLA-B*08, whereas RKTKRNTNR (SEQ ID NO:1051) most probably binds to HLA-B*2705.

[0148] Peptides C64-C70 represent overlapping 15mers spanning the sequence KGGRKPARLIVFPDLGVRVCE (SEQ ID NO:1052). C64 and C70 react with PBMC from donor H32 and H38, respectively. The minimal sequence of the epitope is therefore located within the sequence ARLIVFPDL (SEQ ID NO:1053). Prediction algorithms indicate that ARLIVFPDL (SEQ ID NO:1053) represents a ligand of HLA-HLA-B*2705 and HLA-B*2709.

TABLE-US-00005 TABLE 5 Summary of HCV peptides reactive with PBMC. Donors reactive directly ex vivo in IFN-gamma ELIspot with . . . reactive after 2 rounds HCV-derived peptides of in vitro stimulation Peptide H32 H33 ID G05 G18 H02 H03 H04 H10 H12 H19 SPR H38 H03 H10 SPR H38 1557 20 75 1577 15 30 165 1579 45 35 75 1605 25 1615 30 325 1624 30 55 30 420 1628 40 45 25 20 100 1629 30 70 15 1798 25 115 1799 20 90 1800 35 95 1801 20 20 A3 80 A4 15 A5 110 A7 70 A78 25 A170 35 A212 60 A241 35 B08 55 B38 30 B76 35 C64 30 C70 20 C92 25 C94 25 C97 35 C98 70 C100 60 70 C101 50 C102 20 C106 45 C112 20 C118 35 C120 25 45 105 C134 20 C138 30 Donors reactive directly ex vivo in IFN-gamma ELIspot . . . reactive after 2 with HCV-derived peptides rounds of in vitro stimulation Peptide H32 H33 ID G05 G18 H02 H03 H04 H10 H12 H19 SPR H38 H03 H10 SPR 1557 20 75 1577 15 30 165 1579 45 35 75 1605 25 1615 30 325 1624 30 55 30 420 1628 40 45 25 20 1629 30 70 15 1798 25 115 1799 20 90 1800 35 95 1801 20 20 A3 80 A4 15 A5 110 A7 70 A78 25 A170 35 A212 60 A241 35 B08 55 B38 30 B76 35 C64 30 C70 20 C92 25 C94 25 C97 35 C98 70 C100 60 70 C101 50 C102 20 C106 45 C112 20 C118 35 C120 25 45 105 Numbers represent peptide-specific IFN-gamma secreting T-cells/10.sup.6 PBMC calculated from ELIspot results (duplicate determinations); values > 8 (>3.times. over background) were regarded statistically significant. Donors H32 and H33 are spontaneously recovered patients.

Example V

Binding of HCV Derived Peptides to HLA Class II Molecules

[0149] In addition to the peptides listed in Table 1, several new peptides incorporating sequences from overlapping reactive peptides or avoiding critical residues like cystein were synthesized (Table 4). These were retested for their affinities to class II soluble HLA molecules, and results were compared to those obtained with the original (Table 6).

TABLE-US-00006 TABLE 6 Binding of selected HCV-derived peptides and their 15-mer counterparts to soluble HLA class II molecules SEQ ID Peptide Binding to soluble HLA-DRB1* NO: ID Peptide sequences 0101 0401 0404 0701 1101 1054 1798 IGLGKVLVDILAGYGAGVAGALVAFK - - + ++ +/- 1055 B84 GSIGLGKVLVDILAG + + + 1056 B86 IGLGKVLVDILAGYG + ++ + + 1057 B88 LGKVLVDILAGYGAG + ++ + 1058 B92 LVDILAGYGAGVAGA + - 1059 B94 DILAGYGAGVAGALV + - - - 1060 B96 LAGYGAGVAGALVAF ++ ++ - +/- +/- 1061 1799 AAWYELTPAETTVRLR ++ + + - +/- 1062 B46 AGAAWYELTPALETTV +++ +++ +++ - +/- 1063 B48 AAWYELTPAETTVRL +++ +++ +++ - +/- 1064 1827 TAYSQQTRGLLG ++ - +/- + + 1065 C114 TAYSQQTRGLLGCIV +++ +/- +/- + ++ 1066 1829 SMSYTWTGALITP + - - + +/- 1067 1604 VVCCSMSYTWTGALITPC + + ++ ++ + 1068 1650 VDYPYRLWHYPCTVNFTIFKVRMYVGGVEHRL 1069 A130 DYPYRLWHYPCTVNF + ++ +/- 1070 A131 YPYRLWHYPCTVNFT - 1071 A135 LWHYPCTVNFTIFKV - - ++ 1072 A141 TVNFTIFKVRMYVGG - - +/- ++ 1073 A145 TIFKVRMYVGGVEHR +/- - 1074 1651 VDYPYRLWHYPCTVNYTIFKIRMYVGGVEHRL 1075 1800 DYPYRLWHYPCTVNYTIFKI - - +/- ++ - 1076 A147 DYPYRLWHYPCTVNY - - 1077 A152 LWHYPCTVNYTIFKI - - 1078 A158 TVNYTIFKIRMYVGG - - +/- 1079 A162 TIFKIRMYVGGVEHR +/- - 1080 1817 RMYVGGVEHRL - - +/- 1081 1426 HMWNFISGIQYLAGLSTLPGNPA + + ++ ++ + 1082 1425 NFISGIQYLAGLSTLPGNPA ++ ++ ++ nd nd 1083 1006 MWNFISGIQYLAGLSTLPGN ++ + ++ nd nd ("+++" strong affinity, "++" intermediate affinity, "+" weak affinity, "-+ no affinity, "nd" not done; core binding motifs are underlined)

[0150] Abolished affinities to DRB1*0101 and DRB1*0401 molecules in the case of peptide 1798 in comparison with its shorter counterparts (B84-B96) is probably due to the long sequence (26 amino acids) which can have a secondary structure that prevents binding. It is to be expected that in vivo, upon proteolytic cleavage, peptide 1798 will give rise to two shorter class II epitopes. Removed cystein (C) residues in peptides 1827 and 1829 (derivatives of peptides C114 and 1604, respectively) seem to be crucial for binding to DRB1*0401 molecules but do not essentially change affinities to other tested DR subtypes.

Example VI

Identification and Characterization of HCV-Epitope Hotspots

[0151] Here, a T-cell epitope hotspot (thereafter referred to as "hotspot") is defined as a short peptide sequence at least comprising more than one T-cell epitope. For example, two or more epitopes may be located shortly after each other (shortly being defined as less than 5-10 amino acids), or directly after each other, or partially or even fully over-lapping. Hotspots may contain only class I or class II epitopes, or a combination of both. Epitopes in hotspots may have different HLA restrictions.

[0152] Due to the highly complex and selective pathways of class I and class II antigen processing, referred to in the introduction, T-cell epitopes cannot be easily predicted within the sequence of a polypeptide. Though widely used, computer algorithms for T-cell epitope prediction have a high rate of both false-negatives and false-positives.

[0153] Thus, as even individual T-cell epitopes are not obvious within the sequence of a polypeptide, the same is even more the case for hotspots. Several radically different experimental approaches are combined according to the present invention for T-cell epitope identification, including epitope capture, HLA-transgenic animals and in vitro stimulation of human mononuclear cells. All three approaches are systematically applied on overlapping peptides spanning the antigen of interest, enabling comprehensive identification of epitopes (refer to CMV Epitope Capture patent). Upon such a comprehensive analysis, not limited to a particular HLA allele, but rather unravelling all possibly targeted epitopes within a population, epitope hotspots may become apparent. Within an antigen, only few if any sequences show characteristics of hotspots. Thus the identification of a hotspot is always a surprising event.

[0154] T-cell epitope hotspots offer important advantages: Hotspots can activate and can be recognized by different T-cell clones of a subject. Hotspots (when comprising epitopes with different HLA restriction) can interact with T-cells from different non HLA-matched individuals.

[0155] Epitope-based vaccines, so far have aimed at selected prevalent HLA-alleles, for instance HLA-A2, which is expressed in about half of Caucasians. Since other alleles are less frequent, epitope-based vaccines with broad worldwide population coverage will have to comprise many different epitopes. The number of chemical entities (for instance peptides) of a vaccine is limited by constraints originating from manufacturing, formulation and product stability.

[0156] Hotspots enable such epitope-based vaccines with broad worldwide population coverage, as they provide a potentially high number of epitopes by a limited number of peptides.

TABLE-US-00007 TABLE 7 T-cell epitope hotspots in conserved regions of HCV. peptide ID peptide sequence Class I class II source data 1835 KFPGGGQIVGGVYLLPRRGPRLGVRATRK (SEQ ID NO:1084) A2, A3, B7 DR11 Example III, VI 83 KFPGGGQIVGGVYLLPRRGPRL (SEQ ID NO:1085) A2 B7 DR11 Example VI 1051 YLLPRRGPRL (SEQ ID NO:1086) A2 Bategay 1995 1843 LPRRGPRL (SEQ ID NO:1087) B7 Example III GPRLGVRAT (SEQ ID NO:1088) B7 Koziel 1993 RLGVRATRK (SEQ ID NO:1089) A3 Chang 1999 84 GYKVLVLNPSVAAT (SEQ ID NO:1090) DR1, 4, 7, 11 Tab.2:A200-A206 AYAAQGYKVL (SEQ ID NO:1091) A24 prediction 84EX AYAAQGYKVLVLNPSVAAT (SEQ ID NO:1092) A24 DR1, 4, 7, 11 Example VI 87 DLMGYIPAV (SEQ ID NO:1093) A2 Sarobe 1998 GYIPLVGAPL (SEQ ID NO:1094) A24 prediction 87EX DLMGYIPLVGAPL (SEQ ID NO:1095) A2, A24 Example VI 89 CINGVCWTV (SEQ ID NO:1096) A2 Koziel 1995 1577 GEVQVVSTATQSFLLAT (SEQ ID NO:1097) DR 4, 7 Tab.2 89EX GEVQVVSTATQSFLATCINGVCWTV (SEQ ID NO:1098) A2 DR 4, 7 Example VI 1426 HMWNFISGIQYLAGLSTLPGNPA (SEQ ID NO:1099) A2 DR1, 4, 7, 11 Example VII 1006 MWNFISGIQYLAGLSTLPGN (SEQ ID NO:1100) Example VII 1425 NFISGIQYLAGLSTLPGNPA (SEQ ID NO:1101) Example VII QYLAGLSTL (SEQ ID NO:1102) A24 prediction 1334 HMWNFISGI (SEQ ID NO:1103) A2 Wentworth 1996 1650 VDYPYRLWHYPCTVNFTIFKVRMYVGGVEHRL (SEQ ID NO:1104) Cw7 , A2 , A24, DR1, 4,7,11 Tab.2, 3, 6 A11, A3 Example III 1836 DYPYRLWHYPCTVNFTIFKI (SEQ ID NO:1105) Cw7, A2; A24, DR1, 4, 7, 11 Tab.2, 3, 6 A11 1846 DYPYRLWHYPCTVNFTIFKV (SEQ ID NO:1106) Cw7, A2; A24, DR1, 4, 7, 11 Tab.2, 3, 6 A11 Example III 1651 VDYPYRLWHYPCTVNYTIFKIRMYVGGVEHRL (SEQ ID NO:1107) Tab.2, 3, 6 1800 DYPYRLWHYPCTVNYTIFKI (SEQ ID NO:1108) Cw7, A24, A11 DR7 Tab.2, 5, 6 1754 DYPYRLWHY (SEQ ID NO:1109) Cw7 Lauer 2002 1815 TVNYTIFKI (SEQ ID NO:1110) A11 prediction 1816 TINYTIFK (SEQ ID NO:1111) A11 Koziel 1995 TVNFTIFKV (SEQ ID NO:1112) A11 prediction HYPCTVNYTI (SEQ ID NO:1113) A24 prediction HYPCTVNFTI (SEQ ID NO:1114) A24 prediction RMYVGGVEHR (SEQ ID NO:1115) A3 Chang 1999 1799 AAWYELTPAETTVRLR (SEQ ID NO:1116) B7? B35 DR1, 4 Tab.2, 5, 6 1818 TPAETTVRL (SEQ ID NO:1117) B7? B35 Ibe 1998 1827EX GWRLLAPITAYSQQTRGLLGCIV (SEQ ID NO:1118) A2 ,A3, A24, DR1, 4, 7, 11 Example VI B8 C114 TAYSQQTRGLLGCIV (SEQ ID NO:1119) A24, B8? DR1, 4, 7, 11 Tab.2, 6 1827 TAYSQQTRGLLG (SEQ ID NO:1120) A24, B8? DR1, 7, 11 Tab.6 C112 GQGWRLLAPITAYSQ (SEQ ID NO:1121) A3?, A2?, DR1 Tab.2, 5 RLLAPITAY (SEQ ID NO:1122) A3 prediction C114EX GQGWRLLAPITAYSQQTRGLLGCIV (SEQ ID NO:1123) A24, A3?, A2?, DR1, 4, 7, 11 Tab.2, 5, 6 B8? 1827EX GQGWRLLAPITAYSQQTRGLLG (SEQ ID NO:1124) A24, A3?, A2?, DR1, 7, 11 Tab.2, 5, 6 B8? 1801 AYSQQTRGLL (SEQ ID NO:1125) A24 Tab.5 1819 AYSQQTRGL (SEQ ID NO:1126) A24 Kurokohchi 2001 1798 IGLGKVLVDILAGYGAGVAGALVAFK (SEQ ID NO:1127) A2, 24, 3, 11 DR1, 4, 7 Tab.2, 3, 5, 6 1820 ILAGYGAGV (SEQ ID NO:1128) A2 Bategay 1995 1821 VAGALVAFK (SEQ ID NO:1129) A3, 11 Chang 1999 GYGAGVAGAL (SEQ ID NO:1130) A24 prediction 1604 VVCCSMSYTWTGALITPC (SEQ ID NO:1131) A2, A24, B7 DR1, 4, 7, 11 Tab.2, 3, 6 1829 SMSYTWTGALITP (SEQ ID NO:1132) A2, A24, B7, DR1, 7, 11 Tab.6 SMSYTWTGAL (SEQ ID NO:1133) A2, B7 prediction SYTWTGALI (SEQ ID NO:1134) A24 prediction 1579 FTDNSSPPAVPQTFQV (SEQ ID NO:1135) A1, 2; B7, 51 DR53 = B4*01 Tab.5 1624 LEDRDRSELSPLLLSTTEW (SEQ ID NO:1136) A1, 2, 3, 26 DR7 Tab.2, 3, 5 B8, 27, 4402, 60 1848 LEDRDRSELSPLLLST (SEQ ID NO:1137) A1, 2, 3, 26, DR7 Example VI B8, 27, 44 02, 60 RSELSPLLL (SEQ ID NO:1138) A1 prediction ELSPLLLST (SEQ ID NO:1139) A2, A3 prediction DRDRSELSPL (SEQ ID NO:1140) A26, B27 prediction LEDRDRSEL (SEQ ID NO:1141) B08, B4402 prediction 1824 LEDRDRSEL (SEQ ID NO:1142) B60 Wang 2001 1547 YLVAYQATVCAEAQAPPPSWD (SEQ ID NO:1143) A2 DR1, 4, 7, 11 Tab.2, 3 1822 YLVAYQATV (SEQ ID NO:1144) A2 Wentworth 1996 A1A7 MSTNPKPQRKTKRNTNR (SEQ ID NO:1145) A11, B08, B27 Tab.5 A3A7 PQRKTKRNTNR (SEQ ID NO:1146) B08, B27 Tab.5 QRKTKRNTN (SEQ ID NO:1147) B08 prediction RKTKRNTNR (SEQ ID NO:1148) B2705 prediction MSTNPKPQR (SEQ ID NO:1149) A11 prediction MSTNPKPQK (SEQ ID NO:1150) A11 Wong 1998 A122EX LINTNGSWHINRTALNCNDSL (SEQ ID NO:1151) A2, 2, 3, B8 DR1, 4, 7, 11 Tab.2, 3 A122 NGSWHINRTALNCNDSL (SEQ ID NO:1152) A2 DR1, 4, 7, 11 Tab.2, 3 LINTNGSWHI (SEQ ID NO:1153) A2, 3 prediction RTALNCNDSL (SEQ ID NO:1154) A2 prediction 1825 LINTNGSWHINRTALN (SEQ ID NO:1155) A2, 3, B8 prediction 1826 SWHINRTALN (SEQ ID NO:1156) B8 prediction A241 TTILGIGTVLDQAET (SEQ ID NO:1157) A2, A3 DR1, 4 Tab.2, 5 TTILGIGTV (SEQ ID NO:1158) A2 prediction TILGIGTVL (SEQ ID NO:1159) A3 prediction B8B38 FDSSVLCECYDAGAAWYE (SEQ ID NO:1160) A1, 2, 3, 26 Tab.5 B8 FDSSVLCECYDAGCA (SEQ ID NO:1161) A3, A26 Tab.5 VLCECYDAGA (SEQ ID NO:1162) A2 prediction B38 VVLCECYDAGAAWYE (SEQ ID NO:1163) A1 Tab.5 C70EX ARLIVFPDLGVRVCEKMALY (SEQ ID NO:1164) A2, A3, B27 Tab.5 C64-C70 ARLIVFPDL (SEQ ID NO:1165) B*2705?, *2709? Tab.5 1831 RLIVFPDLGV (SEQ ID NO:1166) A2 Gruener 2000 1832 RVCEKMALY (SEQ ID NO:1167) A3 Wong 1998 C92 AFCSAMYVGDLCGSV (SEQ ID NO:1168) A2, B51 DR1, 4 Tab.2, 5 C97 GVLFGLAYFSHVGNW (SEQ ID NO:1169) A2, 3, 26, DR1, 4, 7 Tab.5 B2705, 51 C106 TRVPYFVRAQGLIRA (SEQ ID NO:1170) A3, 24, DR1, 4, 7 Tab.2, 5 B7 ,B8, B2705 C134 TTLLFNILGGWVAAQ (SEQ ID NO:1171) A2 DR1, 7, 11 Tab.2, 5 1823 LLFNILGGWV (SEQ ID NO:1172) A2 Bategay 1995 Hotspots (incl. some variations) are shown in bold, epitopes contained within the hotspots in normal font. Peptide number and sequence, as well as HLAclass I and class II coverage are given. Source data refers to Examples and Tables within this specification, or literature references.

Example VII

HCV Epitope Hotspot Ipep 1426 Contains at Least HLA-A*0201 and Several Promiscuous Class II T-Cell Epitopes

[0157] The major objective of this experiment was to compare the immunogenicity of the "hospot" Ipep 1426, which contains at least one HLA-A*0201 epitope (Ipep 1334) and 2 promiscuous class II epitopes (Ipeps 1006 and 1425), to the individual epitopes. To this end peripheral blood mononuclear cells (PBMC) from several healthy HLA-typed blood donors were stimulated in vitro either with 1426 or a mixture of 1334, 1006, 1425. Three rounds of stimulation were performed resulting in oligoclonal T cell lines. Then, responses against all four peptides were assessed by interferon-gamma (IFN-.gamma.) ELIspot analysis.

[0158] Peptide 1426, induces T cell responses similarly well as individual epitopes comprised within its sequence. In particular, CD8 positive T cells directed against the HLA-A*0201 restricted epitope 1334 were successfully generated.

TABLE-US-00008 TABLE 8 peptide induced IFN-.gamma. secretion of oligoclonal T cell lines. Donor HLA A*0201, A*03, B7, B60; A*0206, A*01, B27, B50; DRB1*1501, -B1*1302 DRB1*0401, -B1*1402 line raised line raised line raised line raised against against 1006 + against against 1006 + Peptide ID 1426 1425 + 1334 1426 1425 + 1334 1006 ++ ++ ++ ++ 1425 +++ +++ +++ ++ 1334 + + - - 1006 + ++ ++ ++ ++ 1425 + 1334 1426 +++ +++ +++ ++ 84 (HCV - - - - derived negative control) Lines were generated from two HLA-typed healthy individuals by 3 rounds of in vitro priming with either peptide 1426 or a mixture of peptides 1006 + 1425 + 1334. The reactivity of CD4 and CD8 positive T cells in these lines was assessed by IFN-.gamma. ELIspot ("+++" very strong, "++" strong, "+" significant, "-" no IFN-gamma secretion).

REFERENCES

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Sequence CWU 1

1

1172115PRTHepatitis C virus 1Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys1 5 10 15215PRTHepatitis C virus 2Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn1 5 10 15315PRTHepatitis C virus 3Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp1 5 10 15415PRTHepatitis C virus 4Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Ser1 5 10 15515PRTHepatitis C virus 5Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Ser Leu1 5 10 15615PRTHepatitis C virus 6Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser1 5 10 15715PRTHepatitis C virus 7Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val1 5 10 15815PRTHepatitis C virus 8Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg1 5 10 15915PRTHepatitis C virus 9Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu1 5 10 151015PRTHepatitis C virus 10Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu Arg1 5 10 151115PRTHepatitis C virus 11Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu Arg Ala1 5 10 151215PRTHepatitis C virus 12Ala Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val1 5 10 151315PRTHepatitis C virus 13Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg1 5 10 151415PRTHepatitis C virus 14Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu1 5 10 151515PRTHepatitis C virus 15Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly1 5 10 151615PRTHepatitis C virus 16Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr1 5 10 151715PRTHepatitis C virus 17Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly1 5 10 151815PRTHepatitis C virus 18Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala1 5 10 151915PRTHepatitis C virus 19Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly1 5 10 152015PRTHepatitis C virus 20Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val1 5 10 152115PRTHepatitis C virus 21Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala1 5 10 152215PRTHepatitis C virus 22Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly1 5 10 152315PRTHepatitis C virus 23Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala1 5 10 152415PRTHepatitis C virus 24Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Val Met Ser Gly1 5 10 152515PRTHepatitis C virus 25Asp Ile Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val1 5 10 152615PRTHepatitis C virus 26Ile Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala1 5 10 152718PRTHepatitis C virus 27Pro Glu Tyr Asp Leu Glu Leu Ile Thr Ser Cys Ser Ser Asn Val Ser1 5 10 15Val Ala2820PRTHepatitis C virus 28Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Ser Pro Val Val Val Gly1 5 10 15Thr Thr Asp Arg202918PRTHepatitis C virus 29Gly Trp Ala Gly Trp Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Trp1 5 10 15Gly Pro3018PRTHepatitis C virus 30Val Val Cys Cys Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr1 5 10 15Pro Cys3117PRTHepatitis C virus 31Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Val Cys Ala Cys Leu Trp1 5 10 15Met3215PRTHepatitis C virus 32Gly Val Leu Phe Gly Leu Ala Tyr Phe Ser Met Val Gly Asn Trp1 5 10 153321PRTHepatitis C virus 33Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Ala Arg Ala Gln Ala Pro1 5 10 15Pro Pro Ser Trp Asp203415PRTHepatitis C virus 34Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val1 5 10 153515PRTHepatitis C virus 35Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala1 5 10 153615PRTHepatitis C virus 36Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe1 5 10 153715PRTHepatitis C virus 37Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys1 5 10 153815PRTHepatitis C virus 38Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Ile1 5 10 153915PRTHepatitis C virus 39Glu Thr Ala Gly Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro1 5 10 154015PRTHepatitis C virus 40Thr Ala Gly Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro Pro1 5 10 154115PRTHepatitis C virus 41Ala Gly Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro Pro Gly1 5 10 154215PRTHepatitis C virus 42Gly Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro Pro Gly Ser1 5 10 154315PRTHepatitis C virus 43Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Val1 5 10 154415PRTHepatitis C virus 44Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys Ile Met Ser Gly1 5 10 154515PRTHepatitis C virus 45Val Asn Leu Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Val Val1 5 10 154615PRTHepatitis C virus 46His Ala Gly Leu Arg Asp Leu Ala Val Ala Val Glu Pro Val Val1 5 10 154715PRTHepatitis C virus 47Thr Thr Leu Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Ala Gln1 5 10 154815PRTHepatitis C virus 48Val Met Gly Ser Ser Tyr Gly Phe Gln Tyr Ser Pro Gly Gln Arg1 5 10 154917PRTHepatitis C virus 49Val Leu Thr Ser Met Leu Thr Asp Pro Ser His Ile Thr Ala Glu Thr1 5 10 15Ala5017PRTHepatitis C virus 50Val Leu Thr Ser Met Leu Thr Asp Pro Ser His Ile Thr Ala Glu Ala1 5 10 15Ala5116PRTHepatitis C virus 51Gly Glu Val Gln Val Val Ser Thr Ala Thr Gln Ser Phe Leu Ala Thr1 5 10 155216PRTHepatitis C virus 52Gly Glu Val Gln Val Leu Ser Thr Val Thr Gln Ser Phe Leu Gly Thr1 5 10 155315PRTHepatitis C virus 53Ala Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val1 5 10 155415PRTHepatitis C virus 54Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg1 5 10 155515PRTHepatitis C virus 55Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu1 5 10 155621PRTHepatitis C virus 56Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Ala Arg Ala Lys Ala Pro1 5 10 15Pro Pro Ser Trp Asp205715PRTHepatitis C virus 57Gln Thr Val Asp Phe Ser Leu Asp Pro Thr Phe Thr Ile Glu Thr1 5 10 155818PRTHepatitis C virus 58Val Phe Thr Gly Leu Thr His Ile Asp Ala His Phe Leu Ser Gln Thr1 5 10 15Lys Gln5915PRTHepatitis C virus 59Gly Val Leu Ala Gly Leu Ala Tyr Tyr Ser Met Val Gly Asn Trp1 5 10 156015PRTHepatitis C virus 60Tyr Tyr Leu Thr Arg Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala1 5 10 156115PRTHepatitis C virus 61Ser Gly Lys Ser Thr Lys Val Pro Val Ala Tyr Ala Ala Gln Gly1 5 10 156215PRTHepatitis C virus 62Gly Lys Ser Thr Lys Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr1 5 10 156315PRTHepatitis C virus 63Lys Ser Thr Lys Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys1 5 10 156415PRTHepatitis C virus 64Ser Thr Lys Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val1 5 10 156515PRTHepatitis C virus 65Thr Lys Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu1 5 10 156615PRTHepatitis C virus 66Lys Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val1 5 10 156715PRTHepatitis C virus 67Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu1 5 10 156815PRTHepatitis C virus 68Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn1 5 10 156915PRTHepatitis C virus 69Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro1 5 10 157015PRTHepatitis C virus 70Thr Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala1 5 10 157115PRTHepatitis C virus 71Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala Gly1 5 10 157215PRTHepatitis C virus 72Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala Gly Ala1 5 10 157315PRTHepatitis C virus 73Ala Phe Cys Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Ser Val1 5 10 157415PRTHepatitis C virus 74Ala Phe Cys Ser Ala Leu Tyr Val Gly Asp Leu Cys Gly Ser Val1 5 10 157515PRTHepatitis C virus 75Pro Ala Leu Ser Thr Gly Leu Leu His Leu His Gln Asn Ile Val1 5 10 157615PRTHepatitis C virus 76Ser Gly Met Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala1 5 10 157715PRTHepatitis C virus 77Gly Met Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly1 5 10 157815PRTHepatitis C virus 78Met Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala1 5 10 157915PRTHepatitis C virus 79Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala1 5 10 158015PRTHepatitis C virus 80Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp1 5 10 158115PRTHepatitis C virus 81Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp Tyr1 5 10 158215PRTHepatitis C virus 82Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp Tyr Glu1 5 10 158315PRTHepatitis C virus 83Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Ile Met Ser1 5 10 158415PRTHepatitis C virus 84Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Ile Met Ser Gly1 5 10 158515PRTHepatitis C virus 85Gly Val Ala Gly Ala Leu Val Ala Phe Lys Ile Met Ser Gly Glu1 5 10 158615PRTHepatitis C virus 86Thr Thr Leu Leu Leu Asn Ile Leu Gly Gly Trp Leu Ala Ala Gln1 5 10 158715PRTHepatitis C virus 87Ala Val Arg Thr Lys Leu Lys Leu Thr Pro Leu Pro Ala Ala Ser1 5 10 158817PRTHepatitis C virus 88Pro Met Gly Phe Ser Tyr Asp Thr Arg Cys Phe Asp Ser Thr Val Thr1 5 10 15Glu8916PRTHepatitis C virus 89Asn Thr Pro Gly Leu Pro Val Cys Gln Asp His Leu Glu Phe Trp Glu1 5 10 159019PRTHepatitis C virus 90Leu Glu Asp Arg Asp Arg Ser Glu Leu Ser Pro Leu Leu Leu Ser Thr1 5 10 15Thr Glu Trp9120PRTHepatitis C virus 91Thr Val Pro Gln Asp Ala Val Ser Arg Ser Gln Arg Arg Gly Arg Thr1 5 10 15Gly Arg Gly Arg209216PRTHepatitis C virus 92Phe Thr Glu Ala Met Thr Arg Tyr Ser Ala Pro Pro Gly Asp Pro Pro1 5 10 159315PRTHepatitis C virus 93Leu Pro Gly Cys Ser Phe Ser Ile Phe Leu Leu Ala Leu Leu Ser1 5 10 159415PRTHepatitis C virus 94Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser1 5 10 159515PRTHepatitis C virus 95Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu1 5 10 159615PRTHepatitis C virus 96Asp Ile Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val1 5 10 159715PRTHepatitis C virus 97Ile Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala1 5 10 159815PRTHepatitis C virus 98Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe1 5 10 159915PRTHepatitis C virus 99Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys1 5 10 1510015PRTHepatitis C virus 100Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys Ile1 5 10 1510115PRTHepatitis C virus 101Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys Ile Met1 5 10 1510215PRTHepatitis C virus 102Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr1 5 10 1510315PRTHepatitis C virus 103Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val1 5 10 1510415PRTHepatitis C virus 104Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg1 5 10 1510515PRTHepatitis C virus 105Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu1 5 10 1510615PRTHepatitis C virus 106Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu Arg1 5 10 1510715PRTHepatitis C virus 107Gly Gln Gly Trp Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln1 5 10 1510815PRTHepatitis C virus 108Gly Cys Ile Val Val Ser Met Thr Gly Arg Asp Lys Thr Gln Val1 5 10 1510915PRTHepatitis C virus 109Ser Tyr Leu Lys Gly Ser Ser Gly Gly Pro Leu Leu Cys Pro Ser1 5 10 1511015PRTHepatitis C virus 110Thr Gly Glu Ile Pro Phe Tyr Gly Lys Ala Ile Pro Ile Glu Val1 5 10 1511115PRTHepatitis C virus 111Phe Phe Thr Trp Leu Asp Gly Val Gln Ile His Arg Tyr Ala Pro1 5 10 1511215PRTHepatitis C virus 112Asp Leu Pro Gln Ile Ile Glu Arg Leu His Gly Leu Ser Ala Phe1 5 10 1511315PRTHepatitis C virus 113Asp Leu Pro Gln Ile Ile Gln Arg Leu His Gly Leu Ser Ala Phe1 5 10 1511415PRTHepatitis C virus 114Gly Leu Pro Val Ser Ala Leu Arg Gly Arg Glu Ile Leu Leu Gly1 5 10 1511515PRTHepatitis C virus 115Cys Gly Tyr Arg Arg Cys Arg Ala Ser Gly Val Leu Thr Thr Ser1 5 10 1511616PRTHepatitis C virus 116Asn Ala Val Ala Tyr Tyr Arg Gly Leu Asp Val Ser Val Ile Pro Thr1 5 10 1511715PRTHepatitis C virus 117Glu Phe Val Gln Asp Cys Asn Cys Ser Ile Tyr Pro Gly His Val1 5 10 1511815PRTHepatitis C virus 118Pro Thr Ser Gly Asp Val Val Val Val Ala Thr Asp Ala Leu Met1 5 10 1511915PRTHepatitis C virus 119Leu Trp Ala Arg Met Ile Leu Met Thr His Phe Phe Ser Ile Leu1 5 10 1512015PRTHepatitis C virus 120Leu Trp Val Arg Met Val Leu Met Thr His Phe Phe Ser Ile Leu1 5 10 1512115PRTHepatitis C virus 121Glu Thr Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro1 5 10 1512215PRTHepatitis C virus 122Thr Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro1 5 10 1512315PRTHepatitis C virus 123Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly1 5 10 1512415PRTHepatitis C virus 124Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly Ser1 5 10 1512515PRTHepatitis C virus 125Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Val1 5 10

1512618PRTHepatitis C virus 126Val Val Cys Cys Ser Met Ser Tyr Ser Trp Thr Gly Ala Leu Ile Thr1 5 10 15Pro Cys12715PRTHepatitis C virus 127Ala Ala Gly Leu Arg Asp Leu Ala Val Ala Val Glu Pro Ile Val1 5 10 1512815PRTHepatitis C virus 128Ala Val Arg Thr Lys Leu Lys Leu Thr Pro Ile Pro Ala Ala Ser1 5 10 1512937PRTHepatitis C virus 129Gly Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile1 5 10 15Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys20 25 30Ile Met Ser Gly Glu3513015PRTHepatitis C virus 130Pro Val Asn Ser Trp Leu Gly Asn Ile Ile Met Tyr Ala Pro Thr1 5 10 1513115PRTHepatitis C virus 131Pro Val Asn Ser Trp Leu Gly Asn Ile Ile Gln Tyr Ala Pro Thr1 5 10 1513234PRTHepatitis C virus 132Ser Gly Met Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly1 5 10 15Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu Arg20 25 30Ala Tyr13334PRTHepatitis C virus 133Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu1 5 10 15Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Val Ala Ser Met Met20 25 30Ala Phe13419PRTHepatitis C virus 134Leu Thr Pro Pro His Ser Ala Lys Ser Lys Tyr Gly Tyr Gly Ala Lys1 5 10 15Glu Val Arg13516PRTHepatitis C virus 135Thr Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Val Ala Val Thr Gln1 5 10 1513619PRTHepatitis C virus 136Leu Glu Asp Arg Asp Arg Ser Gln Leu Ser Pro Leu Leu His Ser Thr1 5 10 15Thr Glu Trp13736PRTHepatitis C virus 137Asp Pro Arg His Arg Ser Arg Asn Val Gly Lys Val Ile Asp Thr Leu1 5 10 15Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Val Val Gly Ala20 25 30Pro Leu Gly Gly3513832PRTHepatitis C virus 138Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe1 5 10 15Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His Arg Leu20 25 3013932PRTHepatitis C virus 139Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr1 5 10 15Thr Ile Phe Lys Ile Arg Met Tyr Val Gly Gly Val Glu His Arg Leu20 25 3014028PRTHepatitis C virus 140Lys Gly Gly Arg Lys Pro Ala Arg Leu Ile Val Phe Pro Asp Leu Gly1 5 10 15Val Arg Val Cys Glu Lys Met Ala Leu Tyr Asp Val20 2514123PRTHepatitis C virus 141Ile Gln Leu Ile Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala1 5 10 15Leu Asn Cys Asn Asp Ser Leu2014223PRTHepatitis C virus 142Ile Gln Leu Val Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala1 5 10 15Leu Asn Cys Asn Asp Ser Leu2014323PRTHepatitis C virus 143Leu Pro Ala Leu Ser Thr Gly Leu Ile His Leu His Gln Asn Ile Val1 5 10 15Asp Val Gln Tyr Leu Tyr Gly2014420PRTHepatitis C virus 144Ile Lys Gly Gly Arg His Leu Ile Phe Cys His Ser Lys Lys Lys Cys1 5 10 15Asp Glu Leu Ala2014541PRTHepatitis C virus 145Tyr Leu His Ala Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro Val1 5 10 15Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val20 25 30Ala Ala Thr Leu Gly Phe Gly Ala Tyr35 4014615PRTHepatitis C virus 146Ser Ser Met Pro Pro Leu Glu Gly Glu Pro Gly Asp Pro Asp Leu1 5 10 1514719PRTHepatitis C virus 147Leu Thr Pro Pro His Ser Ala Lys Ser Lys Phe Gly Tyr Gly Ala Lys1 5 10 15Asp Val Arg14819PRTHepatitis C virus 148Leu Thr Pro Pro His Ser Ala Arg Ser Lys Tyr Gly Tyr Gly Ala Lys1 5 10 15Glu Val Arg14916PRTHepatitis C virus 149Ser Gly His Arg Met Ala Trp Asp Met Met Met Asn Trp Ser Pro Thr1 5 10 1515016PRTHepatitis C virus 150Thr Gly His Arg Met Ala Trp Asp Met Met Met Asn Trp Ser Pro Thr1 5 10 1515130PRTHepatitis C virus 151Ile Thr Tyr Ser Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser1 5 10 15Gly Gly Ala Tyr Asp Ile Ile Ile Cys Asp Glu Cys His Ser20 25 3015237PRTHepatitis C virus 152Ala Arg Ala Leu Ala His Gly Val Arg Val Leu Glu Asp Gly Val Asn1 5 10 15Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser Phe Ser Ile Phe Leu Leu20 25 30Ala Leu Leu Ser Cys3515328PRTHepatitis C virus 153Lys Gly Gly Lys Lys Ala Ala Arg Leu Ile Val Tyr Pro Asp Leu Gly1 5 10 15Val Arg Val Cys Glu Lys Met Ala Leu Tyr Asp Val20 2515415PRTHepatitis C virus 154Thr Val Asn Phe Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly1 5 10 1515523PRTHepatitis C virus 155His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser1 5 10 15Thr Leu Pro Gly Asn Pro Ala2015667PRTHepatitis C virus 156Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn1 5 10 15Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gly Gly Gln Ile Val Gly20 25 30Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu Gly Val Arg Ala35 40 45Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg Gly Arg Arg Gln Pro50 55 60Ile Pro Lys6515756PRTHepatitis C virus 157Val Asn Leu Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Val Val Gly1 5 10 15Val Val Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly Glu Gly20 25 30Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala Ser Arg Gly Asn35 40 45His Val Ser Pro Thr His Tyr Val50 5515837PRTHepatitis C virus 158Gly Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile1 5 10 15Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys20 25 30Ile Met Ser Gly Glu3515934PRTHepatitis C virus 159Ser Gly Met Phe Asp Ser Ser Val Leu Cys Glu Cys Tyr Asp Ala Gly1 5 10 15Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu Arg20 25 30Ala Tyr16034PRTHepatitis C virus 160Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu1 5 10 15Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala Ser Leu Met20 25 30Ala Phe16116PRTHepatitis C virus 161Phe Ser Asp Asn Ser Thr Pro Pro Ala Val Pro Gln Thr Tyr Gln Val1 5 10 1516256PRTHepatitis C virus 162Val Asn Leu Leu Pro Gly Ile Leu Ser Pro Gly Ala Leu Val Val Gly1 5 10 15Val Ile Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly Glu Gly20 25 30Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala Ser Arg Gly Asn35 40 45His Val Ala Pro Thr His Tyr Val50 551638PRTHepatitis C virus 163Leu Pro Arg Arg Gly Pro Arg Leu1 516410PRTHepatitis C virus 164Ser Pro Gly Ala Leu Val Val Gly Val Ile1 5 101659PRTHepatitis C virus 165Gln Arg Lys Thr Lys Arg Asn Thr Asn1 51668PRTHepatitis C virus 166Gln Arg Lys Thr Lys Arg Asn Thr1 51679PRTHepatitis C virus 167Gln Arg Lys Thr Lys Arg Asn Thr Asn1 51689PRTHepatitis C virus 168Ser Ala Lys Ser Lys Tyr Gly Tyr Gly1 51699PRTHepatitis C virus 169Ser Ala Arg Ser Lys Tyr Gly Tyr Gly1 51709PRTHepatitis C virus 170Arg Lys Thr Lys Arg Asn Thr Asn Arg1 517129PRTHepatitis C virus 171Lys Phe Pro Gly Gly Gly Gln Ile Val Gly Gly Val Tyr Leu Leu Pro1 5 10 15Arg Arg Gly Pro Arg Leu Gly Val Arg Ala Thr Arg Lys20 2517219PRTHepatitis C virus 172Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val1 5 10 15Ala Ala Thr17313PRTHepatitis C virus 173Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala Pro Leu1 5 1017425PRTHepatitis C virus 174Gly Glu Val Gln Val Val Ser Thr Ala Thr Gln Ser Phe Leu Ala Thr1 5 10 15Cys Ile Asn Gly Val Cys Trp Thr Val20 2517520PRTHepatitis C virus 175Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe Thr1 5 10 15Ile Phe Lys Ile2017620PRTHepatitis C virus 176Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe Thr1 5 10 15Ile Phe Lys Val2017720PRTHepatitis C virus 177Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr Thr1 5 10 15Ile Phe Lys Ile2017816PRTHepatitis C virus 178Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu Arg1 5 10 1517912PRTHepatitis C virus 179Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Leu Gly1 5 1018025PRTHepatitis C virus 180Gly Gln Gly Trp Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln Gln1 5 10 15Thr Arg Gly Leu Leu Gly Cys Ile Val20 2518123PRTHepatitis C virus 181Gly Trp Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln Gln Thr Arg1 5 10 15Gly Leu Leu Gly Cys Ile Val2018226PRTHepatitis C virus 182Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala1 5 10 15Gly Val Ala Gly Ala Leu Val Ala Phe Lys20 2518313PRTHepatitis C virus 183Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr Pro1 5 1018416PRTHepatitis C virus 184Phe Thr Asp Asn Ser Ser Pro Pro Ala Val Pro Gln Thr Phe Gln Val1 5 10 1518516PRTHepatitis C virus 185Leu Glu Asp Arg Asp Arg Ser Glu Leu Ser Pro Leu Leu Leu Ser Thr1 5 10 1518617PRTHepatitis C virus 186Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn1 5 10 15Arg18721PRTHepatitis C virus 187Leu Ile Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn1 5 10 15Cys Asn Asp Ser Leu2018816PRTHepatitis C virus 188Leu Ile Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn1 5 10 1518915PRTHepatitis C virus 189Thr Thr Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr1 5 10 1519018PRTHepatitis C virus 190Phe Asp Ser Ser Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp1 5 10 15Tyr Glu19120PRTHepatitis C virus 191Ala Arg Leu Ile Val Phe Pro Asp Leu Gly Val Arg Val Cys Glu Lys1 5 10 15Met Ala Leu Tyr2019215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 192Ser Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly Tyr Lys Val1 5 10 1519315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 193Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu1 5 10 1519415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 194Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val1 5 10 1519515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 195Val Pro Ala Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu1 5 10 1519615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 196Pro Ala Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn1 5 10 1519715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 197Ala Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro1 5 10 1519815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 198Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser1 5 10 1519915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 199Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val1 5 10 1520015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 200Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala1 5 10 1520115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 201Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala1 5 10 1520215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 202Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr1 5 10 1520315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 203Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr1 5 10 1520415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 204Ser Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn1 5 10 1520515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 205Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn Arg1 5 10 1520615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 206Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn Arg Arg1 5 10 1520715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 207Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn Arg Arg Pro1 5 10 1520815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 208Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn Arg Arg Pro Gln1 5 10 1520915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 209Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn Arg Arg Pro Gln Asp1 5 10 1521015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 210Gln Arg Lys Thr Lys Arg Asn Thr Asn Arg Arg Pro Gln Asp Val1 5 10 1521115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 211Arg Lys Thr Lys Arg Asn Thr Asn Arg Arg Pro Gln Asp Val Lys1 5 10 1521215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 212Lys Thr Lys Arg Asn Thr Asn Arg Arg Pro Gln Asp Val Lys Phe1 5 10 1521315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 213Thr Lys Arg Asn Thr Asn Arg Arg Pro Gln Asp Val Lys Phe Pro1 5 10 1521415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 214Lys Arg Asn Thr Asn Arg Arg Pro Gln Asp Val Lys Phe Pro Gly1 5 10 1521515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 215Arg Asn Thr Asn Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gly1 5 10 1521615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 216Asn Thr Asn Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gly Gly1 5 10 1521715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 217Thr Asn Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gly Gly Gln1 5 10 1521815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 218Asn Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gly Gly Gln Ile1 5 10 1521915PRTArtificial SequenceDescription of Artificial Sequence

Synthetic Peptide 219Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gly Gly Gln Ile Val1 5 10 1522015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 220Arg Pro Gln Asp Val Lys Phe Pro Gly Gly Gly Gln Ile Val Gly1 5 10 1522115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 221Pro Gln Asp Val Lys Phe Pro Gly Gly Gly Gln Ile Val Gly Gly1 5 10 1522215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 222Gln Asp Val Lys Phe Pro Gly Gly Gly Gln Ile Val Gly Gly Val1 5 10 1522315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 223Asp Val Lys Phe Pro Gly Gly Gly Gln Ile Val Gly Gly Val Tyr1 5 10 1522415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 224Val Lys Phe Pro Gly Gly Gly Gln Ile Val Gly Gly Val Tyr Leu1 5 10 1522515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 225Lys Phe Pro Gly Gly Gly Gln Ile Val Gly Gly Val Tyr Leu Leu1 5 10 1522615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 226Phe Pro Gly Gly Gly Gln Ile Val Gly Gly Val Tyr Leu Leu Pro1 5 10 1522715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 227Pro Gly Gly Gly Gln Ile Val Gly Gly Val Tyr Leu Leu Pro Arg1 5 10 1522815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 228Gly Gly Gly Gln Ile Val Gly Gly Val Tyr Leu Leu Pro Arg Arg1 5 10 1522915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 229Gly Gly Gln Ile Val Gly Gly Val Tyr Leu Leu Pro Arg Arg Gly1 5 10 1523015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 230Gly Gln Ile Val Gly Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro1 5 10 1523115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 231Gln Ile Val Gly Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg1 5 10 1523215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 232Ile Val Gly Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu1 5 10 1523315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 233Val Gly Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu Gly1 5 10 1523415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 234Gly Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu Gly Val1 5 10 1523515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 235Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu Gly Val Arg1 5 10 1523615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 236Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu Gly Val Arg Ala1 5 10 1523714PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 237Tyr Leu Pro Arg Arg Gly Pro Arg Leu Gly Val Arg Ala Thr1 5 1023814PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 238Leu Leu Pro Arg Arg Gly Pro Arg Leu Gly Val Arg Ala Thr1 5 1023914PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 239Leu Pro Arg Arg Gly Pro Arg Leu Gly Val Arg Ala Thr Arg1 5 1024015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 240Pro Arg Arg Gly Pro Arg Leu Gly Val Arg Ala Thr Arg Lys Thr1 5 10 1524115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 241Arg Arg Gly Pro Arg Leu Gly Val Arg Ala Thr Arg Lys Thr Ser1 5 10 1524215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 242Arg Gly Pro Arg Leu Gly Val Arg Ala Thr Arg Lys Thr Ser Glu1 5 10 1524315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 243Gly Pro Arg Leu Gly Val Arg Ala Thr Arg Lys Thr Ser Glu Arg1 5 10 1524415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 244Pro Arg Leu Gly Val Arg Ala Thr Arg Lys Thr Ser Glu Arg Ser1 5 10 1524515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 245Arg Leu Gly Val Arg Ala Thr Arg Lys Thr Ser Glu Arg Ser Gln1 5 10 1524615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 246Leu Gly Val Arg Ala Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro1 5 10 1524715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 247Gly Val Arg Ala Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg1 5 10 1524815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 248Val Arg Ala Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg Gly1 5 10 1524915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 249Arg Ala Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg Gly Arg1 5 10 1525015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 250Ala Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg Gly Arg Arg1 5 10 1525115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 251Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg Gly Arg Arg Gln1 5 10 1525215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 252Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg Gly Arg Arg Gln Pro1 5 10 1525315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 253Lys Thr Ser Glu Arg Ser Gln Pro Arg Gly Arg Arg Gln Pro Ile1 5 10 1525415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 254Thr Ser Glu Arg Ser Gln Pro Arg Gly Arg Arg Gln Pro Ile Pro1 5 10 1525515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 255Ser Glu Arg Ser Gln Pro Arg Gly Arg Arg Gln Pro Ile Pro Lys1 5 10 1525615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 256Asp Pro Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Ile Asp Thr1 5 10 1525715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 257Pro Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Leu1 5 10 1525815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 258Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Leu Thr1 5 10 1525915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 259Arg Arg Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Leu Thr Cys1 5 10 1526015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 260Arg Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Leu Thr Cys Gly1 5 10 1526115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 261Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Leu Thr Cys Gly Phe1 5 10 1526215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 262Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Leu Thr Cys Gly Phe1 5 10 1526315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 263Asn Leu Gly Lys Val Ile Asp Thr Leu Thr Cys Gly Phe Ala Asp1 5 10 1526415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 264Leu Gly Lys Val Ile Asp Thr Leu Thr Cys Gly Phe Ala Asp Leu1 5 10 1526515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 265Gly Lys Val Ile Asp Thr Leu Thr Cys Gly Phe Ala Asp Leu Met1 5 10 1526615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 266Lys Val Ile Asp Thr Leu Thr Cys Gly Phe Ala Asp Leu Met Gly1 5 10 1526715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 267Val Ile Asp Thr Leu Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr1 5 10 1526815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 268Ile Asp Thr Leu Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile1 5 10 1526915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 269Asp Thr Leu Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro1 5 10 1527015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 270Thr Leu Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu1 5 10 1527115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 271Leu Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu Val1 5 10 1527215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 272Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu Val Gly1 5 10 1527315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 273Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala1 5 10 1527415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 274Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala Pro1 5 10 1527515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 275Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala Pro Leu1 5 10 1527615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 276Ala Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala Pro Leu Gly1 5 10 1527715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 277Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala Pro Leu Gly Gly1 5 10 1527815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 278Asp Pro Arg His Arg Ser Arg Asn Val Gly Lys Val Ile Asp Thr1 5 10 1527915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 279Pro Arg His Arg Ser Arg Asn Val Gly Lys Val Ile Asp Thr Leu1 5 10 1528014PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 280Arg His Arg Ser Arg Asn Val Gly Lys Ile Asp Thr Leu Thr1 5 1028115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 281His Arg Ser Arg Asn Val Gly Lys Val Ile Asp Thr Leu Thr Cys1 5 10 1528215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 282Arg Ser Arg Asn Val Gly Lys Val Ile Asp Thr Leu Thr Cys Gly1 5 10 1528315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 283Ser Arg Asn Val Gly Lys Val Ile Asp Thr Leu Thr Cys Gly Phe1 5 10 1528415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 284Arg Asn Val Gly Lys Val Ile Asp Thr Leu Thr Cys Gly Phe Ala1 5 10 1528515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 285Asn Val Gly Lys Val Ile Asp Thr Leu Thr Cys Gly Phe Ala Asp1 5 10 1528615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 286Val Gly Lys Val Ile Asp Thr Leu Thr Cys Gly Phe Ala Asp Leu1 5 10 1528715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 287Thr Leu Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Val1 5 10 1528815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 288Leu Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Val Val1 5 10 1528915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 289Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Val Val Gly1 5 10 1529015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 290Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Val Val Gly Ala1 5 10 1529115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 291Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Val Val Gly Ala Pro1 5 10 1529215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 292Phe Ala Asp Leu Met Gly Tyr Ile Pro Val Val Gly Ala Pro Leu1 5 10 1529315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 293Ala Asp Leu Met Gly Tyr Ile Pro Val Val Gly Ala Pro Leu Gly1 5 10 1529415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 294Asp Leu Met Gly Tyr Ile Pro Val Val Gly Ala Pro Leu Gly Gly1 5 10 1529515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 295Ala Arg Ala Leu Ala His Gly Val Arg Val Leu Glu Asp Gly Val1 5 10 1529615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 296Arg Ala Leu Ala His Gly Val Arg Val Leu Glu Asp Gly Val Asn1 5 10 1529715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 297Ala Leu Ala His Gly Val Arg Val Leu Glu Asp Gly Val Asn Tyr1 5 10 1529815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 298Leu Ala His Gly Val Arg Val Leu Glu Asp Gly Val Asn Tyr Ala1 5 10 1529915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 299Ala His Gly Val Arg Val Leu Glu Asp Gly Val Asn Tyr Ala Thr1 5 10 1530015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 300His Gly Val Arg Val Leu Glu Asp Gly Val Asn Tyr Ala Thr Gly1 5 10 1530115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 301Gly Val Arg Val Leu Glu Asp Gly Val Asn Tyr Ala Thr Gly Asn1 5 10 1530215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 302Val Arg Val Leu Glu Asp Gly Val Asn Tyr Ala Thr Gly Asn Leu1 5 10 1530315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 303Arg

Val Leu Glu Asp Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro1 5 10 1530415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 304Val Leu Glu Asp Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gly1 5 10 1530516PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 305Leu Glu Asp Gly Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gly Cys1 5 10 1530615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 306Glu Asp Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser1 5 10 1530715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 307Asp Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser Phe1 5 10 1530815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 308Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser Phe Ser1 5 10 1530915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 309Val Asn Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser Phe Ser Ile1 5 10 1531015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 310Asn Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser Phe Ser Ile Phe1 5 10 1531115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 311Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser Phe Ser Ile Phe Leu1 5 10 1531215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 312Ala Thr Gly Asn Leu Pro Gly Cys Ser Phe Ser Ile Phe Leu Leu1 5 10 1531315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 313Thr Gly Asn Leu Pro Gly Cys Ser Phe Ser Ile Phe Leu Leu Ala1 5 10 1531415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 314Gly Asn Leu Pro Gly Cys Ser Phe Ser Ile Phe Leu Leu Ala Leu1 5 10 1531515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 315Asn Leu Pro Gly Cys Ser Phe Ser Ile Phe Leu Leu Ala Leu Leu1 5 10 1531615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 316Leu Pro Gly Cys Ser Phe Ser Ile Phe Leu Leu Ala Leu Leu Ser1 5 10 1531715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 317Pro Gly Cys Ser Phe Ser Ile Phe Leu Leu Ala Leu Leu Ser Cys1 5 10 1531815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 318Ile Gln Leu Ile Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr1 5 10 1531915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 319Gln Leu Ile Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala1 5 10 1532015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 320Leu Ile Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu1 5 10 1532114PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 321Ile Asn Thr Asn Gly Ser Trp Ile Asn Arg Thr Ala Leu Asn1 5 1032215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 322Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys1 5 10 1532315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 323Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn1 5 10 1532415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 324Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp1 5 10 1532515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 325Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Ser1 5 10 1532615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 326Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Ser Leu1 5 10 1532715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 327Ile Gln Leu Val Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr1 5 10 1532815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 328Gln Leu Val Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala1 5 10 1532915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 329Leu Val Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu1 5 10 1533015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 330Val Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn1 5 10 1533115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 331Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn1 5 10 1533215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 332Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe1 5 10 1533315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 333Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe Thr1 5 10 1533415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 334Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe Thr Ile1 5 10 1533515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 335Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe Thr Ile Phe1 5 10 1533615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 336Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe Thr Ile Phe Lys1 5 10 1533715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 337Leu Trp His Tyr Pro Cys Thr Val Asn Phe Thr Ile Phe Lys Val1 5 10 1533815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 338Trp His Tyr Pro Cys Thr Val Asn Phe Thr Ile Phe Lys Val Arg1 5 10 1533915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 339His Tyr Pro Cys Thr Val Asn Phe Thr Ile Phe Lys Val Arg Met1 5 10 1534015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 340Tyr Pro Cys Thr Val Asn Phe Thr Ile Phe Lys Val Arg Met Tyr1 5 10 1534115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 341Pro Cys Thr Val Asn Phe Thr Ile Phe Lys Val Arg Met Tyr Val1 5 10 1534215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 342Cys Thr Val Asn Phe Thr Ile Phe Lys Val Arg Met Tyr Val Gly1 5 10 1534315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 343Thr Val Asn Phe Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly1 5 10 1534415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 344Val Asn Phe Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val1 5 10 1534515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 345Asn Phe Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu1 5 10 1534615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 346Phe Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His1 5 10 1534715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 347Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His Arg1 5 10 1534815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 348Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His Arg Leu1 5 10 1534915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 349Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr1 5 10 1535015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 350Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr Thr1 5 10 1535115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 351Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr Thr Ile1 5 10 1535215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 352Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr Thr Ile Phe1 5 10 1535315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 353Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr Thr Ile Phe Lys1 5 10 1535415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 354Leu Trp His Tyr Pro Cys Thr Val Asn Tyr Thr Ile Phe Lys Ile1 5 10 1535515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 355Trp His Tyr Pro Cys Thr Val Asn Tyr Thr Ile Phe Lys Ile Arg1 5 10 1535615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 356His Tyr Pro Cys Thr Val Asn Tyr Thr Ile Phe Lys Ile Arg Met1 5 10 1535715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 357Tyr Pro Cys Thr Val Asn Tyr Thr Ile Phe Lys Ile Arg Met Tyr1 5 10 1535815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 358Pro Cys Thr Val Asn Tyr Thr Ile Phe Lys Ile Arg Met Tyr Val1 5 10 1535915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 359Cys Thr Val Asn Tyr Thr Ile Phe Lys Ile Arg Met Tyr Val Gly1 5 10 1536015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 360Thr Val Asn Tyr Thr Ile Phe Lys Ile Arg Met Tyr Val Gly Gly1 5 10 1536115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 361Val Asn Tyr Thr Ile Phe Lys Ile Arg Met Tyr Val Gly Gly Val1 5 10 1536215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 362Asn Tyr Thr Ile Phe Lys Ile Arg Met Tyr Val Gly Gly Val Glu1 5 10 1536315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 363Tyr Thr Ile Phe Lys Ile Arg Met Tyr Val Gly Gly Val Glu His1 5 10 1536415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 364Thr Ile Phe Lys Ile Arg Met Tyr Val Gly Gly Val Glu His Arg1 5 10 1536515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 365Ile Phe Lys Ile Arg Met Tyr Val Gly Gly Val Glu His Arg Leu1 5 10 1536615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 366Leu Pro Ala Leu Ser Thr Gly Leu Ile His Leu His Gln Asn Ile1 5 10 1536714PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 367Pro Ala Leu Ser Thr Gly Ile His Leu His Gln Asn Ile Val1 5 1036815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 368Ala Leu Ser Thr Gly Leu Ile His Leu His Gln Asn Ile Val Asp1 5 10 1536914PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 369Leu Ser Thr Gly Ile His Leu His Gln Asn Ile Val Asp Val1 5 1037015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 370Ser Thr Gly Leu Ile His Leu His Gln Asn Ile Val Asp Val Gln1 5 10 1537115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 371Thr Gly Leu Ile His Leu His Gln Asn Ile Val Asp Val Gln Tyr1 5 10 1537215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 372Gly Leu Ile His Leu His Gln Asn Ile Val Asp Val Gln Tyr Leu1 5 10 1537315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 373Leu Ile His Leu His Gln Asn Ile Val Asp Val Gln Tyr Leu Tyr1 5 10 1537415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 374Ile His Leu His Gln Asn Ile Val Asp Val Gln Tyr Leu Tyr Gly1 5 10 1537515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 375Leu Pro Ala Leu Ser Thr Gly Leu Leu His Leu His Gln Asn Ile1 5 10 1537615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 376Pro Ala Leu Ser Thr Gly Leu Leu His Leu His Gln Asn Ile Val1 5 10 1537715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 377Ala Leu Ser Thr Gly Leu Leu His Leu His Gln Asn Ile Val Asp1 5 10 1537815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 378Leu Ser Thr Gly Leu Leu His Leu His Gln Asn Ile Val Asp Val1 5 10 1537915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 379Ser Thr Gly Leu Leu His Leu His Gln Asn Ile Val Asp Val Gln1 5 10 1538015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 380Thr Gly Leu Leu His Leu His Gln Asn Ile Val Asp Val Gln Tyr1 5 10 1538115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 381Gly Leu Leu His Leu His Gln Asn Ile Val Asp Val Gln Tyr Met1 5 10 1538215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 382Leu Leu His Leu His Gln Asn Ile Val Asp Val Gln Tyr Met Tyr1 5 10 1538315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 383Leu His Leu His Gln Asn Ile Val Asp Val Gln Tyr Met Tyr Gly1 5 10 1538415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 384His Leu His Ala Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro1 5 10 1538515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 385Leu His Ala Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro Ala1 5 10 1538615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 386His Ala Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro Ala Ala1 5 10 1538715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 387Ala Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro

Ala Ala Tyr1 5 10 1538815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 388Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro Ala Ala Tyr Ala1 5 10 1538915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 389Thr Gly Ser Gly Lys Ser Thr Lys Val Pro Ala Ala Tyr Ala Ala1 5 10 1539015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 390Gly Ser Gly Lys Ser Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln1 5 10 1539115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 391Ser Gly Lys Ser Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly1 5 10 1539215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 392Gly Lys Ser Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly Tyr1 5 10 1539315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 393Lys Ser Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly Tyr Lys1 5 10 1539415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 394Ser Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly Tyr Lys Val1 5 10 1539515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 395Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu1 5 10 1539615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 396Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val1 5 10 1539715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 397Val Pro Ala Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu1 5 10 1539815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 398Pro Ala Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn1 5 10 1539915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 399Ala Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro1 5 10 1540015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 400Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser1 5 10 1540115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 401Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val1 5 10 1540215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 402Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala1 5 10 1540315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 403Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala1 5 10 1540415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 404Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr1 5 10 1540515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 405Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr Leu1 5 10 1540615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 406Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr Leu Gly1 5 10 1540715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 407Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr Leu Gly Phe1 5 10 1540815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 408Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr Leu Gly Phe Gly1 5 10 1540915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 409Leu Val Leu Asn Pro Ser Val Ala Ala Thr Leu Gly Phe Gly Ala1 5 10 1541015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 410Val Leu Asn Pro Ser Val Ala Ala Thr Leu Gly Phe Gly Ala Tyr1 5 10 1541115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 411Tyr Leu His Ala Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro1 5 10 1541215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 412Leu His Ala Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro Val1 5 10 1541315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 413His Ala Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro Val Ala1 5 10 1541415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 414Ala Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro Val Ala Tyr1 5 10 1541515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 415Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro Val Ala Tyr Ala1 5 10 1541615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 416Thr Gly Ser Gly Lys Ser Thr Lys Val Pro Val Ala Tyr Ala Ala1 5 10 1541715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 417Gly Ser Gly Lys Ser Thr Lys Val Pro Val Ala Tyr Ala Ala Gln1 5 10 1541815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 418Ser Gly Lys Ser Thr Lys Val Pro Val Ala Tyr Ala Ala Gln Gly1 5 10 1541915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 419Gly Lys Ser Thr Lys Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr1 5 10 1542015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 420Lys Ser Thr Lys Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys1 5 10 1542115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 421Ser Thr Lys Val Pro Val Ala Tyr Ala Ala Gln Gly Thr Lys Val1 5 10 1542215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 422Thr Lys Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu1 5 10 1542315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 423Lys Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val1 5 10 1542415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 424Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu1 5 10 1542515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 425Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn1 5 10 1542615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 426Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro1 5 10 1542714PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 427Ile Thr Ser Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys1 5 1042815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 428Thr Tyr Ser Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser1 5 10 1542915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 429Tyr Ser Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gly1 5 10 1543015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 430Ser Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gly Gly1 5 10 1543115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 431Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gly Gly Ala1 5 10 1543215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 432Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gly Gly Ala Tyr1 5 10 1543315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 433Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gly Gly Ala Tyr Asp1 5 10 1543415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 434Lys Phe Leu Ala Asp Gly Gly Cys Ser Gly Gly Ala Tyr Asp Ile1 5 10 1543515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 435Phe Leu Ala Asp Gly Gly Cys Ser Gly Gly Ala Tyr Asp Ile Ile1 5 10 1543615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 436Leu Ala Asp Gly Gly Cys Ser Gly Gly Ala Tyr Asp Ile Ile Ile1 5 10 1543715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 437Ala Asp Gly Gly Cys Ser Gly Gly Ala Tyr Asp Ile Ile Ile Cys1 5 10 1543815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 438Asp Gly Gly Cys Ser Gly Gly Ala Tyr Asp Ile Ile Ile Cys Asp1 5 10 1543915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 439Gly Gly Cys Ser Gly Gly Ala Tyr Asp Ile Ile Ile Cys Asp Glu1 5 10 1544015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 440Gly Cys Ser Gly Gly Ala Tyr Asp Ile Ile Ile Cys Asp Glu Cys1 5 10 1544115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 441Cys Ser Gly Gly Ala Tyr Asp Ile Ile Ile Cys Asp Glu Cys His1 5 10 1544215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 442Ser Gly Gly Ala Tyr Asp Ile Ile Ile Cys Asp Glu Cys His Ser1 5 10 1544315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 443Thr Thr Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr1 5 10 1544415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 444Thr Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala1 5 10 1544515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 445Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala Gly1 5 10 1544615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 446Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala Gly Ala1 5 10 1544715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 447Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala Gly Ala Arg1 5 10 1544815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 448Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala Gly Ala Arg Leu1 5 10 1544915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 449Gly Thr Val Leu Asp Gln Ala Glu Thr Ala Gly Ala Arg Leu Val1 5 10 1545015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 450Thr Val Leu Asp Gln Ala Glu Thr Ala Gly Ala Arg Leu Val Val1 5 10 1545115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 451Val Leu Asp Gln Ala Glu Thr Ala Gly Ala Arg Leu Val Val Leu1 5 10 1545215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 452Leu Asp Gln Ala Glu Thr Ala Gly Ala Arg Leu Val Val Leu Ala1 5 10 1545315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 453Asp Gln Ala Glu Thr Ala Gly Ala Arg Leu Val Val Leu Ala Thr1 5 10 1545415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 454Gln Ala Glu Thr Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala1 5 10 1545515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 455Ala Glu Thr Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr1 5 10 1545615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 456Glu Thr Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro1 5 10 1545715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 457Thr Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro1 5 10 1545815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 458Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly1 5 10 1545915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 459Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly Ser1 5 10 1546015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 460Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Val1 5 10 1546115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 461Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Val Thr1 5 10 1546215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 462Thr Ser Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr1 5 10 1546315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 463Ser Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala1 5 10 1546415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 464Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala Gly Val1 5 10 1546515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 465Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala Gly Val Arg1 5 10 1546615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 466Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala Gly Val Arg Leu1 5 10 1546715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 467Gly Thr Val Leu Asp Gln Ala Glu Thr Ala Gly Val Arg Leu Thr1 5 10 1546815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 468Thr Val Leu Asp Gln Ala Glu Thr Ala Gly Val Arg Leu Thr Val1 5 10 1546915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 469Val Leu Asp Gln Ala Glu Thr Ala Gly Val Arg Leu Thr Val Leu1 5 10 1547015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 470Leu Asp Gln Ala Glu Thr Ala Gly Val Arg Leu Thr Val Leu Ala1 5 10 1547115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 471Asp

Gln Ala Glu Thr Ala Gly Val Arg Leu Thr Val Leu Ala Thr1 5 10 1547215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 472Gln Ala Glu Thr Ala Gly Val Arg Leu Thr Val Leu Ala Thr Ala1 5 10 1547315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 473Ala Glu Thr Ala Gly Val Arg Leu Thr Val Leu Ala Thr Ala Thr1 5 10 1547415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 474Glu Thr Ala Gly Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro1 5 10 1547515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 475Thr Ala Gly Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro Pro1 5 10 1547615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 476Ala Gly Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro Pro Gly1 5 10 1547715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 477Gly Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro Pro Gly Ser1 5 10 1547815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 478Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Val1 5 10 1547915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 479Ser Gly Met Phe Asp Ser Ser Val Leu Cys Glu Cys Tyr Asp Ala1 5 10 1548015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 480Gly Met Phe Asp Ser Ser Val Leu Cys Glu Cys Tyr Asp Ala Gly1 5 10 1548115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 481Met Phe Asp Ser Ser Val Leu Cys Glu Cys Tyr Asp Ala Gly Cys1 5 10 1548214PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 482Phe Asp Ser Ser Val Leu Cys Glu Cys Asp Ala Gly Cys Ala1 5 1048315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 483Asp Ser Ser Val Leu Cys Glu Cys Tyr Asp Ala Gly Cys Ala Trp1 5 10 1548415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 484Ser Ser Val Leu Cys Glu Cys Tyr Asp Ala Gly Cys Ala Trp Tyr1 5 10 1548515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 485Ser Val Leu Cys Glu Cys Tyr Asp Ala Gly Cys Ala Trp Tyr Glu1 5 10 1548615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 486Val Leu Cys Glu Cys Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu1 5 10 1548715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 487Leu Cys Glu Cys Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr1 5 10 1548815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 488Cys Glu Cys Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro1 5 10 1548914PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 489Glu Cys Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Ala1 5 1049015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 490Cys Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu1 5 10 1549115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 491Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr1 5 10 1549215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 492Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr1 5 10 1549315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 493Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val1 5 10 1549415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 494Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg1 5 10 1549515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 495Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu1 5 10 1549615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 496Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu Arg1 5 10 1549715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 497Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu Arg Ala1 5 10 1549815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 498Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu Arg Ala Tyr1 5 10 1549915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 499Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser1 5 10 1550015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 500Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val1 5 10 1550115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 501Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg1 5 10 1550215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 502Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu1 5 10 1550315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 503Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu Arg1 5 10 1550415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 504Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu Arg Ala1 5 10 1550515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 505Gly Met Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly1 5 10 1550615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 506Ser Gly Met Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala1 5 10 1550715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 507Gly Met Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly1 5 10 1550815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 508Met Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala1 5 10 1550915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 509Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala1 5 10 1551015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 510Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp1 5 10 1551115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 511Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp Tyr1 5 10 1551215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 512Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp Tyr Glu1 5 10 1551315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 513Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp Tyr Glu Leu1 5 10 1551415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 514Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp Tyr Glu Leu Thr1 5 10 1551515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 515Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp Tyr Glu Leu Thr Pro1 5 10 1551615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 516Glu Cys Tyr Asp Ala Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala1 5 10 1551715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 517Cys Tyr Asp Ala Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu1 5 10 1551815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 518Tyr Asp Ala Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr1 5 10 1551915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 519Asp Ala Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr1 5 10 1552015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 520Ala Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val1 5 10 1552115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 521Gly Ala Ala Trp Tyr Glu Leu Thr Ile Pro Ala Glu Thr Thr Val1 5 10 1552214PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 522Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg1 5 1052314PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 523Asp Ala Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr1 5 1052414PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 524Ala Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser1 5 1052515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 525Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg1 5 10 1552615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 526Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu1 5 10 1552715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 527Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr1 5 10 1552815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 528Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu1 5 10 1552915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 529Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala1 5 10 1553015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 530Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly1 5 10 1553115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 531His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu1 5 10 1553215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 532Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser1 5 10 1553315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 533Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr1 5 10 1553415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 534Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr Leu1 5 10 1553515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 535Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr Leu Pro1 5 10 1553615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 536Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly1 5 10 1553715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 537Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn1 5 10 1553815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 538Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro1 5 10 1553915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 539Ile Gln Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala1 5 10 1554015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 540Gln Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile1 5 10 1554115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 541Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala1 5 10 1554215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 542Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala Ser1 5 10 1554315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 543Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala Ser Ile1 5 10 1554415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 544Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala Ser Leu Met1 5 10 1554515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 545Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala Ser Leu Met Ala1 5 10 1554615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 546Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala Ser Leu Met Ala Phe1 5 10 1554715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 547Gln Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Val1 5 10 1554815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 548Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Val Ala1 5 10 1554915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 549Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Val Ala Ser1 5 10 1555015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 550Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Val Ala Ser Met1 5 10 1555115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 551Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Val Ala Ser Met Met1 5 10 1555215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 552Leu Ser Thr Leu Pro Gly Asn Pro Ala Val Ala Ser Met Met Ala1 5 10 1555315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 553Ser Thr Leu Pro Gly Asn Pro Ala Val Ala Ser Met Met Ala Phe1 5 10 1555415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 554Gly Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp1 5 10 1555515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 555Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile1 5

10 1555614PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 556Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu Asp Ile Leu1 5 1055715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 557Val Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala1 5 10 1555815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 558Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly1 5 10 1555915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 559Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr1 5 10 1556015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 560Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly1 5 10 1556115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 561Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala1 5 10 1556215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 562Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly1 5 10 1556315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 563Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val1 5 10 1556415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 564Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala1 5 10 1556515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 565Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly1 5 10 1556615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 566Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala1 5 10 1556715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 567Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu1 5 10 1556815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 568Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val1 5 10 1556915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 569Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala1 5 10 1557015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 570Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe1 5 10 1557115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 571Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys1 5 10 1557215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 572Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Ile1 5 10 1557315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 573Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Ile Met1 5 10 1557415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 574Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Ile Met Ser1 5 10 1557515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 575Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Ile Met Ser Gly1 5 10 1557615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 576Gly Val Ala Gly Ala Leu Val Ala Phe Lys Ile Met Ser Gly Glu1 5 10 1557715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 577Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Val1 5 10 1557815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 578Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Val Met1 5 10 1557915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 579Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Val Met Ser1 5 10 1558015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 580Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Val Met Ser Gly1 5 10 1558115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 581Gly Val Ala Gly Ala Leu Val Ala Phe Lys Val Met Ser Gly Glu1 5 10 1558215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 582Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Ile1 5 10 1558315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 583Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Ile Ser1 5 10 1558415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 584Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly1 5 10 1558515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 585Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala1 5 10 1558615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 586Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu1 5 10 1558715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 587Asp Ile Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val1 5 10 1558815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 588Ile Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala1 5 10 1558915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 589Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe1 5 10 1559015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 590Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys1 5 10 1559115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 591Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys Ile1 5 10 1559215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 592Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys Ile Met1 5 10 1559315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 593Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys Ile Met Ser1 5 10 1559415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 594Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys Ile Met Ser Gly1 5 10 1559515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 595Gly Ile Ser Gly Ala Leu Val Ala Phe Lys Ile Met Ser Gly Glu1 5 10 1559615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 596Val Asn Leu Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Val Val1 5 10 1559714PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 597Asn Leu Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Trp Gly1 5 1059815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 598Leu Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Val Val Gly Val1 5 10 1559915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 599Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Val Val Gly Val Val1 5 10 1560015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 600Pro Ala Ile Leu Ser Pro Gly Ala Leu Val Val Gly Val Val Cys1 5 10 1560115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 601Ala Ile Leu Ser Pro Gly Ala Leu Val Val Gly Val Val Cys Ala1 5 10 1560215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 602Ile Leu Ser Pro Gly Ala Leu Val Val Gly Val Val Cys Ala Ala1 5 10 1560315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 603Leu Ser Pro Gly Ala Leu Val Val Gly Val Val Cys Ala Ala Ile1 5 10 1560415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 604Ser Pro Gly Ala Leu Val Val Gly Val Val Cys Ala Ala Ile Leu1 5 10 1560515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 605Pro Gly Ala Leu Val Val Gly Val Val Cys Ala Ala Ile Leu Arg1 5 10 1560615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 606Gly Ala Leu Val Val Gly Val Val Cys Ala Ala Ile Leu Arg Arg1 5 10 1560715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 607Ala Leu Val Val Gly Val Val Cys Ala Ala Ile Leu Arg Arg His1 5 10 1560814PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 608Leu Val Val Gly Trp Cys Ala Ala Ile Leu Arg Arg His Val1 5 1060915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 609Val Val Gly Val Val Cys Ala Ala Ile Leu Arg Arg His Val Gly1 5 10 1561015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 610Val Gly Val Val Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro1 5 10 1561115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 611Gly Val Val Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly1 5 10 1561215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 612Val Val Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly Glu1 5 10 1561315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 613Val Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly Glu Gly1 5 10 1561415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 614Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly Glu Gly Ala1 5 10 1561515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 615Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly Glu Gly Ala Val1 5 10 1561615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 616Ala Ile Leu Arg Arg His Val Gly Pro Gly Glu Gly Ala Val Gln1 5 10 1561715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 617Ile Leu Arg Arg His Val Gly Pro Gly Glu Gly Ala Val Gln Trp1 5 10 1561815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 618Leu Arg Arg His Val Gly Pro Gly Glu Gly Ala Val Gln Trp Met1 5 10 1561915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 619Arg Arg His Val Gly Pro Gly Glu Gly Ala Val Gln Trp Met Asn1 5 10 1562015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 620Arg His Val Gly Pro Gly Glu Gly Ala Val Gln Trp Met Asn Arg1 5 10 1562115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 621His Val Gly Pro Gly Glu Gly Ala Val Gln Trp Met Asn Arg Leu1 5 10 1562215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 622Val Gly Pro Gly Glu Gly Ala Val Gln Trp Met Asn Arg Leu Ile1 5 10 1562315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 623Gly Pro Gly Glu Gly Ala Val Gln Trp Met Asn Arg Leu Ile Ala1 5 10 1562415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 624Pro Gly Glu Gly Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe1 5 10 1562515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 625Gly Glu Gly Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala1 5 10 1562615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 626Glu Gly Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala Ser1 5 10 1562715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 627Gly Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala Ser Arg1 5 10 1562815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 628Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala Ser Arg Gly1 5 10 1562916PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 629Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala Ser Arg Asn Gly Asn1 5 10 1563015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 630Gln Trp Met Asn Arg Leu Ile Ala Phe Ala Ser Arg Gly Asn His1 5 10 1563115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 631Trp Met Asn Arg Leu Ile Ala Phe Ala Ser Arg Gly Asn His Val1 5 10 1563214PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 632Met Asn Arg Leu Ala Phe Ala Ser Arg Gly Asn His Val Ser1 5 1063315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 633Asn Arg Leu Ile Ala Phe Ala Ser Arg Gly Asn His Val Ser Pro1 5 10 1563415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 634Arg Leu Ile Ala Phe Ala Ser Arg Gly Asn His Val Ser Pro Thr1 5 10 1563515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 635Leu Ile Ala Phe Ala Ser Arg Gly Asn His Val Ser Pro Thr His1 5 10 1563615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 636Ile Ala Phe Ala Ser Arg Gly Asn His Val Ser Pro Thr His Tyr1 5 10 1563715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 637Ala Phe Ala Ser Arg Gly Asn His Val Ser Pro Thr His Tyr Val1 5 10 1563815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 638Val Asn Leu Leu Pro Gly Ile Leu Ser Pro Gly Ala Leu Val Val1 5 10 1563915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 639Asn Leu Leu Pro Gly Ile Leu Ser Pro Gly Ala Leu Val Val Gly1 5 10 1564015PRTArtificial

SequenceDescription of Artificial Sequence Synthetic Peptide 640Leu Leu Pro Gly Ile Leu Ser Pro Gly Ala Leu Val Val Gly Val1 5 10 1564115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 641Leu Pro Gly Ile Leu Ser Pro Gly Ala Leu Val Val Gly Val Ile1 5 10 1564215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 642Pro Gly Ile Leu Ser Pro Gly Ala Leu Val Val Gly Val Ile Cys1 5 10 1564315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 643Gly Ile Leu Ser Pro Gly Ala Leu Val Val Gly Val Ile Cys Ala1 5 10 1564415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 644Ile Leu Ser Pro Gly Ala Leu Val Val Gly Val Ile Cys Ala Ala1 5 10 1564515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 645Leu Ser Pro Gly Ala Leu Val Val Gly Val Ile Cys Ala Ala Ile1 5 10 1564615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 646Ser Pro Gly Ala Leu Val Val Gly Val Ile Cys Ala Ala Ile Leu1 5 10 1564715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 647Pro Gly Ala Leu Val Val Gly Val Ile Cys Ala Ala Ile Leu Arg1 5 10 1564815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 648Gly Ala Leu Val Val Gly Val Ile Cys Ala Ala Ile Leu Arg Arg1 5 10 1564915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 649Ala Leu Val Val Gly Val Ile Cys Ala Ala Ile Leu Arg Arg His1 5 10 1565015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 650Leu Val Val Gly Val Ile Cys Ala Ala Ile Leu Arg Arg His Val1 5 10 1565115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 651Val Val Gly Val Ile Cys Ala Ala Ile Leu Arg Arg His Val Gly1 5 10 1565215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 652Val Gly Val Ile Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro1 5 10 1565315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 653Gly Val Ile Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly1 5 10 1565415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 654Val Ile Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly Glu1 5 10 1565514PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 655Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly Glu Gly1 5 1065615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 656Met Asn Arg Leu Ile Ala Phe Ala Ser Arg Gly Asn His Val Ala1 5 10 1565715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 657Asn Arg Leu Ile Ala Phe Ala Ser Arg Gly Asn His Val Ala Pro1 5 10 1565815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 658Arg Leu Ile Ala Phe Ala Ser Arg Gly Asn His Val Ala Pro Thr1 5 10 1565915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 659Leu Ile Ala Phe Ala Ser Arg Gly Asn His Val Ala Pro Thr His1 5 10 1566015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 660Ile Ala Phe Ala Ser Arg Gly Asn His Val Ala Pro Thr His Tyr1 5 10 1566115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 661Ala Phe Ala Ser Arg Gly Asn His Val Ala Pro Thr His Tyr Val1 5 10 1566215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 662Lys Gly Gly Arg Lys Pro Ala Arg Leu Ile Val Phe Pro Asp Leu1 5 10 1566315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 663Gly Gly Arg Lys Pro Ala Arg Leu Ile Val Phe Pro Asp Leu Gly1 5 10 1566415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 664Gly Arg Lys Pro Ala Arg Leu Ile Val Phe Pro Asp Leu Gly Val1 5 10 1566515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 665Arg Lys Pro Ala Arg Leu Ile Val Phe Pro Asp Leu Gly Val Arg1 5 10 1566615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 666Lys Pro Ala Arg Leu Ile Val Phe Pro Asp Leu Gly Val Arg Val1 5 10 1566715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 667Pro Ala Arg Leu Ile Val Phe Pro Asp Leu Gly Val Arg Val Cys1 5 10 1566815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 668Ala Arg Leu Ile Val Phe Pro Asp Leu Gly Val Arg Val Cys Glu1 5 10 1566915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 669Arg Leu Ile Val Phe Pro Asp Leu Gly Val Arg Val Cys Glu Lys1 5 10 1567015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 670Leu Ile Val Phe Pro Asp Leu Gly Val Arg Val Cys Glu Lys Met1 5 10 1567115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 671Ile Val Phe Pro Asp Leu Gly Val Arg Val Cys Glu Lys Met Ala1 5 10 1567215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 672Val Phe Pro Asp Leu Gly Val Arg Val Cys Glu Lys Met Ala Leu1 5 10 1567315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 673Phe Pro Asp Leu Gly Val Arg Val Cys Glu Lys Met Ala Leu Tyr1 5 10 1567415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 674Pro Asp Leu Gly Val Arg Val Cys Glu Lys Met Ala Leu Tyr Asp1 5 10 1567515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 675Asp Leu Gly Val Arg Val Cys Glu Lys Met Ala Leu Tyr Asp Val1 5 10 1567615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 676Lys Gly Gly Lys Lys Ala Ala Arg Leu Ile Val Tyr Pro Asp Leu1 5 10 1567715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 677Gly Gly Lys Lys Ala Ala Arg Leu Ile Val Tyr Pro Asp Leu Gly1 5 10 1567815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 678Gly Lys Lys Ala Ala Arg Leu Ile Val Tyr Pro Asp Leu Gly Val1 5 10 1567915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 679Lys Lys Ala Ala Arg Leu Ile Val Tyr Pro Asp Leu Gly Val Arg1 5 10 1568015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 680Lys Ala Ala Arg Leu Ile Val Tyr Pro Asp Leu Gly Val Arg Val1 5 10 1568115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 681Ala Ala Arg Leu Ile Val Tyr Pro Asp Leu Gly Val Arg Val Cys1 5 10 1568215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 682Ala Arg Leu Ile Val Tyr Pro Asp Leu Gly Val Arg Val Cys Glu1 5 10 1568315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 683Arg Leu Ile Val Tyr Pro Asp Leu Gly Val Arg Val Cys Glu Lys1 5 10 1568415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 684Leu Ile Val Tyr Pro Asp Leu Gly Val Arg Val Cys Glu Lys Met1 5 10 1568514PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 685Ile Val Pro Asp Leu Gly Val Arg Val Cys Glu Lys Met Ala1 5 1068615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 686Val Tyr Pro Asp Leu Gly Val Arg Val Cys Glu Lys Met Ala Leu1 5 10 1568715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 687Tyr Pro Asp Leu Gly Val Arg Val Cys Glu Lys Met Ala Leu Tyr1 5 10 1568815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 688Ala Gln Pro Gly Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Leu1 5 10 1568915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 689Gly Gln Pro Gly Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Leu1 5 10 1569015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 690Ala Phe Cys Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Ser Val1 5 10 1569115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 691Ala Phe Cys Ser Ala Leu Tyr Val Gly Asp Leu Cys Gly Ser Val1 5 10 1569215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 692Glu Thr Val Gln Asp Cys Asn Cys Ser Ile Tyr Pro Gly His Val1 5 10 1569315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 693Glu Phe Val Gln Asp Cys Asn Cys Ser Ile Tyr Pro Gly His Val1 5 10 1569415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 694Gly Val Leu Ala Gly Leu Ala Tyr Tyr Ser Met Val Gly Asn Trp1 5 10 1569515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 695Gly Val Leu Phe Gly Leu Ala Tyr Phe Ser Met Val Gly Asn Trp1 5 10 1569615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 696Asp Gln Arg Pro Tyr Cys Trp His Tyr Ala Pro Arg Pro Cys Gly1 5 10 1569714PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 697Asp Gln Arg Pro Tyr Cys Trp Tyr Pro Pro Arg Pro Cys Gly1 5 1069815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 698Thr Cys Pro Thr Asp Cys Phe Arg Lys His Pro Glu Ala Thr Tyr1 5 10 1569915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 699Tyr Thr Lys Cys Gly Ser Gly Pro Trp Leu Thr Pro Arg Cys Leu1 5 10 1570015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 700Leu Asn Ala Ala Cys Asn Trp Thr Arg Gly Glu Arg Cys Asp Leu1 5 10 1570115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 701Leu Asn Ala Ala Cys Asn Phe Thr Arg Gly Glu Arg Cys Asp Leu1 5 10 1570215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 702Ile Ala Gln Ala Glu Ala Ala Leu Glu Asn Leu Val Val Leu Asn1 5 10 1570315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 703Ile Ala Gln Ala Glu Ala Ala Leu Glu Lys Leu Val Val Leu His1 5 10 1570415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 704Thr Arg Val Pro Tyr Phe Val Arg Ala Gln Gly Leu Ile Arg Ala1 5 10 1570515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 705Thr Arg Val Pro Tyr Phe Val Arg Ala His Gly Leu Ile Arg Ala1 5 10 1570615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 706His Ala Gly Leu Arg Asp Leu Ala Val Ala Val Glu Pro Val Val1 5 10 1570715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 707Ala Ala Gly Leu Arg Asp Leu Ala Val Ala Val Glu Pro Ile Val1 5 10 1570815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 708Ile Thr Trp Gly Ala Asp Thr Ala Ala Cys Gly Asp Ile Ile Leu1 5 10 1570915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 709Ile Thr Trp Gly Ala Glu Thr Ala Ala Cys Gly Asp Ile Ile Leu1 5 10 1571015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 710Gly Gln Gly Trp Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln1 5 10 1571115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 711Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Leu Gly Cys Ile Ile1 5 10 1571215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 712Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Leu Gly Cys Ile Val1 5 10 1571315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 713Gly Cys Ile Ile Thr Ser Leu Thr Gly Arg Asp Lys Asn Gln Val1 5 10 1571415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 714Gly Cys Ile Val Val Ser Met Thr Gly Arg Asp Lys Thr Gln Val1 5 10 1571515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 715Val Asn Gly Val Cys Trp Thr Val Tyr His Gly Ala Gly Ser Lys1 5 10 1571615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 716Lys Gly Pro Ile Thr Gln Met Tyr Thr Asn Val Asp Gln Asp Leu1 5 10 1571715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 717Lys Gly Pro Ile Thr Gln Met Tyr Ser Ser Ala Glu Gln Asp Leu1 5 10 1571815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 718Gly Asp Ser Arg Gly Ser Leu Leu Ser Pro Arg Pro Val Ser Tyr1 5 10 1571915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 719Gly Asp Ser Arg Gly Ala Leu Leu Ser Pro Arg Pro Val Ser Tyr1 5 10 1572015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 720Ser Tyr Leu Lys Gly Ser Ser Gly Gly Pro Leu Leu Cys Pro Ser1 5 10 1572115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 721Ser Tyr Leu Lys Gly Ser Ser Gly Gly Pro Val Leu Cys Pro Ser1 5 10 1572215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 722Gly His Ala Val Gly Ile Phe Arg Ala Ala Val Cys Thr Arg Gly1 5 10 1572315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 723Gly Val Asp Pro Asn Ile Arg Thr Gly Val Arg Thr Ile Thr Thr1 5 10 1572415PRTArtificial SequenceDescription of Artificial Sequence

Synthetic Peptide 724Val Pro His Pro Asn Ile Glu Glu Val Ala Leu Ser Asn Thr Gly1 5 10 1572515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 725Thr Gly Glu Ile Pro Phe Tyr Gly Lys Ala Ile Pro Ile Glu Val1 5 10 1572615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 726Thr Gly Glu Ile Pro Phe Tyr Gly Lys Ala Ile Pro Leu Glu Val1 5 10 1572715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 727Pro Thr Ser Gly Asp Val Val Val Val Ala Thr Asp Ala Leu Met1 5 10 1572815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 728Gln Thr Val Asp Phe Ser Leu Asp Pro Thr Phe Thr Ile Glu Thr1 5 10 1572915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 729Thr Leu His Gly Pro Thr Pro Leu Leu Tyr Arg Leu Gly Ala Val1 5 10 1573015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 730Val Gln Asn Glu Val Thr Leu Thr His Pro Ile Thr Lys Tyr Ile1 5 10 1573115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 731Leu Tyr Arg Glu Phe Asp Glu Met Glu Glu Cys Ala Ser His Leu1 5 10 1573215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 732Thr Thr Leu Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Ala Gln1 5 10 1573314PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 733Thr Thr Leu Leu Asn Ile Leu Gly Gly Trp Leu Ala Ala Gln1 5 1073415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 734Pro Ser Ala Ala Ser Ala Phe Val Gly Ala Gly Ile Ala Gly Ala1 5 10 1573515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 735Pro Ser Ala Ala Thr Gly Phe Val Val Ser Gly Leu Ala Gly Ala1 5 10 1573615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 736Thr Pro Cys Ser Gly Ser Trp Leu Arg Asp Val Trp Asp Trp Ile1 5 10 1573715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 737Val Ala Ala Glu Glu Tyr Val Glu Val Thr Arg Val Gly Asp Phe1 5 10 1573815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 738Val Ala Ala Glu Glu Tyr Ala Glu Val Thr Arg His Gly Asp Phe1 5 10 1573915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 739Phe Phe Thr Glu Val Asp Gly Val Arg Leu His Arg Tyr Ala Pro1 5 10 1574015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 740Phe Phe Thr Glu Leu Asp Gly Val Arg Leu His Arg Tyr Ala Pro1 5 10 1574115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 741Phe Phe Thr Trp Val Asp Gly Val Gln Ile His Arg Tyr Ala Pro1 5 10 1574215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 742Phe Phe Thr Trp Leu Asp Gly Val Gln Ile His Arg Tyr Ala Pro1 5 10 1574315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 743Tyr Leu Val Gly Ser Gln Leu Pro Cys Glu Pro Glu Pro Asp Val1 5 10 1574415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 744Tyr Leu Val Gly Ser Gln Leu Pro Cys Asp Pro Glu Pro Asp Val1 5 10 1574515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 745Leu Pro Thr Trp Ala Arg Pro Asp Tyr Asn Pro Pro Leu Leu Glu1 5 10 1574615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 746Ala Ser Leu Arg Gln Lys Lys Val Thr Phe Asp Arg Leu Gln Val1 5 10 1574715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 747Ala Ser Leu Arg Ala Lys Lys Val Thr Phe Asp Arg Leu Gln Val1 5 10 1574815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 748His Ile Arg Ser Val Trp Lys Asp Leu Leu Glu Asp Thr Glu Thr1 5 10 1574915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 749Ile Asp Thr Thr Ile Met Ala Lys Asn Glu Val Phe Cys Val Gln1 5 10 1575015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 750Val Met Gly Ser Ser Tyr Gly Phe Gln Tyr Ser Pro Gly Gln Arg1 5 10 1575115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 751Asp Cys Thr Met Leu Val Cys Gly Asp Asp Leu Val Val Ile Cys1 5 10 1575214PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 752Asp Cys Thr Met Leu Val Asn Gly Asp Asp Leu Trp Ile Cys1 5 1075315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 753Asp Pro Thr Met Leu Val Cys Gly Asp Asp Leu Val Val Ile Cys1 5 10 1575414PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 754Asp Pro Thr Met Leu Val Asn Gly Asp Asp Leu Trp Ile Cys1 5 1075515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 755Leu Trp Ala Arg Met Ile Leu Met Thr His Phe Phe Ser Ile Leu1 5 10 1575615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 756Leu Trp Val Arg Met Val Leu Met Thr His Phe Phe Ser Ile Leu1 5 10 1575715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 757Asp Leu Pro Gln Ile Ile Glu Arg Leu His Gly Leu Ser Ala Phe1 5 10 1575815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 758Asp Leu Pro Gln Ile Ile Gln Arg Leu His Gly Leu Ser Ala Phe1 5 10 1575915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 759Ala Val Arg Thr Lys Leu Lys Leu Thr Pro Ile Pro Ala Ala Ser1 5 10 1576015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 760Ala Val Arg Thr Lys Leu Lys Leu Thr Pro Leu Pro Ala Ala Ser1 5 10 1576115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 761Ser Gly Gly Asp Ile Tyr His Ser Leu Ser Arg Ala Arg Pro Arg1 5 10 1576215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 762Ser Gly Gly Asp Ile Tyr His Ser Val Ser Arg Ala Arg Pro Arg1 5 10 1576315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 763Trp Gly Glu Asn Glu Thr Asp Val Leu Leu Leu Asn Asn Thr Arg1 5 10 1576415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 764Gly Glu Asn Glu Thr Asp Val Leu Leu Leu Asn Asn Thr Arg Pro1 5 10 1576515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 765Trp Phe Gly Cys Thr Trp Met Asn Ser Thr Gly Phe Thr Lys Thr1 5 10 1576615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 766Phe Gly Cys Thr Trp Met Asn Ser Thr Gly Phe Thr Lys Thr Cys1 5 10 1576715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 767Gly Cys Thr Trp Met Asn Ser Thr Gly Phe Thr Lys Thr Cys Gly1 5 10 1576815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 768Gly Leu Pro Val Ser Ala Arg Arg Gly Arg Glu Ile Leu Leu Gly1 5 10 1576915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 769Leu Pro Val Ser Ala Arg Arg Gly Arg Glu Ile Leu Leu Gly Pro1 5 10 1577015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 770Pro Val Ser Ala Arg Arg Gly Arg Glu Ile Leu Leu Gly Pro Ala1 5 10 1577115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 771Val Ser Ala Arg Arg Gly Arg Glu Ile Leu Leu Gly Pro Ala Asp1 5 10 1577215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 772Gly Leu Pro Val Ser Ala Leu Arg Gly Arg Glu Ile Leu Leu Gly1 5 10 1577315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 773Leu Pro Val Ser Ala Leu Arg Gly Arg Glu Ile Leu Leu Gly Pro1 5 10 1577415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 774Pro Val Ser Ala Leu Arg Gly Arg Glu Ile Leu Leu Gly Pro Ala1 5 10 1577515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 775Val Ser Ala Leu Arg Gly Arg Glu Ile Leu Leu Gly Pro Ala Asp1 5 10 1577615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 776Pro Asp Arg Glu Val Leu Tyr Arg Glu Phe Asp Glu Met Glu Glu1 5 10 1577715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 777Asp Arg Glu Val Leu Tyr Arg Glu Phe Asp Glu Met Glu Glu Cys1 5 10 1577815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 778Arg Glu Val Leu Tyr Arg Glu Phe Asp Glu Met Glu Glu Cys Ala1 5 10 1577915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 779Glu Val Leu Tyr Arg Glu Phe Asp Glu Met Glu Glu Cys Ala Ser1 5 10 1578015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 780Val Leu Tyr Arg Glu Phe Asp Glu Met Glu Glu Cys Ala Ser His1 5 10 1578115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 781Leu Tyr Arg Glu Phe Asp Glu Met Glu Glu Cys Ala Ser His Leu1 5 10 1578215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 782Tyr Tyr Leu Thr Arg Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala1 5 10 1578315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 783Tyr Leu Thr Arg Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Trp1 5 10 1578415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 784Leu Thr Arg Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Trp Glu1 5 10 1578515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 785Thr Arg Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Trp Glu Thr1 5 10 1578615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 786Arg Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Trp Glu Thr Ala1 5 10 1578715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 787Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Trp Glu Thr Ala Arg1 5 10 1578814PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 788Pro Thr Thr Pro Leu Ala Arg Ala Trp Glu Thr Ala Arg His1 5 1078915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 789Tyr Tyr Leu Thr Arg Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala1 5 10 1579015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 790Tyr Leu Thr Arg Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Trp1 5 10 1579115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 791Leu Thr Arg Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Trp Glu1 5 10 1579215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 792Thr Arg Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Trp Glu Thr1 5 10 1579315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 793Arg Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Trp Glu Thr Val1 5 10 1579415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 794Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Trp Glu Thr Val Arg1 5 10 1579515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 795Pro Thr Thr Pro Leu Ala Arg Ala Ala Trp Glu Thr Val Arg His1 5 10 1579667PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 796Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn1 5 10 15Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gly Gly Gln Ile Val Gly20 25 30Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu Gly Val Arg Ala35 40 45Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg Gly Arg Arg Gln Pro50 55 60Ile Pro Lys6579756PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 797Val Asn Leu Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Val Val Gly1 5 10 15Val Val Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly Glu Gly20 25 30Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala Ser Arg Gly Asn35 40 45His Val Ser Pro Thr His Tyr Val50 5579820PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 798Ile Lys Gly Gly Arg His Leu Ile Phe Cys His Ser Lys Lys Lys Cys1 5 10 15Asp Glu Leu Ala2079920PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 799Thr Val Pro Gln Asp Ala Val Ser Arg Ser Gln Arg Arg Gly Arg Thr1 5 10 15Gly Arg Gly Arg2080021PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 800Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Ala Arg Ala Gln Ala Pro1 5 10 15Pro Pro Ser Trp Asp2080141PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 801His Leu His Ala Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro Ala1 5 10 15Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val20 25 30Ala Ala Thr Leu Gly Phe Gly Ala Tyr35 4080241PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 802Tyr Leu His Ala Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro Val1 5 10 15Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val20 25 30Ala Ala Thr Leu Gly Phe Gly Ala Tyr35 4080337PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 803Gly Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile1 5 10 15Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe

Lys20 25 30Ile Met Ser Gly Glu3580437PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 804Gly Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile1 5 10 15Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys20 25 30Val Met Ser Gly Glu3580537PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 805Gly Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile1 5 10 15Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys20 25 30Ile Met Ser Gly Glu3580616PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 806Phe Thr Glu Ala Met Thr Arg Tyr Ser Ala Pro Pro Gly Asp Pro Pro1 5 10 1580715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 807Ser Ser Met Pro Pro Leu Glu Gly Glu Pro Gly Asp Pro Asp Leu1 5 10 1580815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 808Cys Gly Tyr Arg Arg Cys Arg Ala Ser Gly Val Leu Thr Thr Ser1 5 10 1580915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 809Pro Val Asn Ser Trp Leu Gly Asn Ile Ile Met Tyr Ala Pro Thr1 5 10 1581015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 810Pro Val Asn Ser Trp Leu Gly Asn Ile Ile Gln Tyr Ala Pro Thr1 5 10 1581134PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 811Ser Gly Met Phe Asp Ser Ser Val Leu Cys Glu Cys Tyr Asp Ala Gly1 5 10 15Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu Arg20 25 30Ala Tyr81234PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 812Ser Gly Met Phe Asp Ser Ser Val Leu Cys Glu Cys Tyr Asp Ala Gly1 5 10 15Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu Arg20 25 30Ala Tyr81334PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 813Ser Gly Met Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly1 5 10 15Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu Arg20 25 30Ala Tyr81434PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 814Ser Gly Met Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly1 5 10 15Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu Arg20 25 30Ala Tyr81534PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 815Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu1 5 10 15Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala Ser Leu Met20 25 30Ala Phe81616PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 816Gly Glu Val Gln Val Val Ser Thr Ala Thr Gln Ser Phe Leu Ala Thr1 5 10 1581716PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 817Gly Glu Val Gln Val Leu Ser Thr Val Thr Gln Ser Phe Leu Gly Thr1 5 10 1581816PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 818Phe Thr Asp Asn Ser Ser Pro Pro Ala Val Pro Gln Thr Phe Gln Val1 5 10 1581916PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 819Phe Ser Asp Asn Ser Thr Pro Pro Ala Val Pro Gln Thr Tyr Gln Val1 5 10 1582016PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 820Asn Ala Val Ala Tyr Tyr Arg Gly Leu Asp Val Ser Val Ile Pro Thr1 5 10 1582156PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 821Val Asn Leu Leu Pro Gly Ile Leu Ser Pro Gly Ala Leu Val Val Gly1 5 10 15Val Ile Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly Glu Gly20 25 30Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala Ser Arg Gly Asn35 40 45His Val Ala Pro Thr His Tyr Val50 5582233PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 822Thr Thr Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala1 5 10 15Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Val20 25 30Thr82333PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 823Thr Ser Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala1 5 10 15Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Val20 25 30Thr82433PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 824Thr Ser Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala1 5 10 15Gly Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Val20 25 30Thr82533PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 825Thr Thr Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala1 5 10 15Gly Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Val20 25 30Thr82634PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 826Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu1 5 10 15Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Val Ala Ser Met Met20 25 30Ala Phe82718PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 827Val Phe Thr Gly Leu Thr His Ile Asp Ala His Phe Leu Ser Gln Thr1 5 10 15Lys Gln82818PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 828Val Val Cys Cys Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr1 5 10 15Pro Cys82918PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 829Val Val Cys Cys Ser Met Ser Tyr Ser Trp Thr Gly Ala Leu Ile Thr1 5 10 15Pro Cys83017PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 830Val Leu Thr Ser Met Leu Thr Asp Pro Ser His Ile Thr Ala Glu Thr1 5 10 15Ala83117PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 831Val Leu Thr Ser Met Leu Thr Asp Pro Ser His Ile Thr Ala Glu Ala1 5 10 15Ala83219PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 832Ala Ser Ser Ser Ala Ser Gln Leu Ser Ala Pro Ser Leu Arg Ala Thr1 5 10 15Cys Thr Thr83319PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 833Leu Thr Pro Pro His Ser Ala Arg Ser Lys Phe Gly Tyr Gly Ala Lys1 5 10 15Asp Val Arg83419PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 834Leu Thr Pro Pro His Ser Ala Asp Ser Lys Phe Gly Tyr Gly Ala Lys1 5 10 15Asp Val Arg83519PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 835Leu Thr Pro Pro His Ser Ala Lys Ser Lys Tyr Gly Tyr Gly Ala Lys1 5 10 15Glu Val Arg83619PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 836Leu Thr Pro Pro His Ser Ala Arg Ser Lys Tyr Gly Tyr Gly Ala Lys1 5 10 15Glu Val Arg83717PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 837Pro Met Gly Phe Ser Tyr Asp Thr Arg Cys Phe Asp Ser Thr Val Thr1 5 10 15Glu83817PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 838Pro Met Gly Phe Ala Tyr Asp Thr Arg Cys Phe Asp Ser Thr Val Thr1 5 10 15Glu83916PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 839Thr Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Thr Cys Val Thr Gln1 5 10 1584016PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 840Thr Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Val Ala Val Thr Gln1 5 10 1584116PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 841Asn Thr Pro Gly Leu Pro Val Cys Gln Asp His Leu Glu Phe Trp Glu1 5 10 1584221PRTArtificial Sequencemodified_res(14)xaa = can be any naturally occurring amino acid 842Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Ala Arg Ala Xaa Ala Pro1 5 10 15Pro Pro Ser Trp Asp2084319PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 843Leu Glu Asp Arg Asp Arg Ser Glu Leu Ser Pro Leu Leu Leu Ser Thr1 5 10 15Thr Glu Trp84419PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 844Leu Glu Asp Arg Asp Arg Ser Gln Leu Ser Pro Leu Leu His Ser Thr1 5 10 15Thr Glu Trp84519PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 845Ala Ser Ser Ser Ala Ser Gln Leu Ser Ala Pro Ser Leu Lys Ala Thr1 5 10 15Cys Thr Thr84618PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 846Pro Glu Tyr Asp Leu Glu Leu Ile Thr Ser Cys Ser Ser Asn Val Ser1 5 10 15Val Ala84720PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 847Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Ser Pro Val Val Val Gly1 5 10 15Thr Thr Asp Arg2084818PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 848Gly Trp Ala Gly Trp Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Trp1 5 10 15Gly Pro84917PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 849Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Val Cys Ala Cys Leu Trp1 5 10 15Met85016PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 850Ser Gly His Arg Met Ala Trp Asp Met Met Met Asn Trp Ser Pro Thr1 5 10 1585116PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 851Thr Gly His Arg Met Ala Trp Asp Met Met Met Asn Trp Ser Pro Thr1 5 10 1585230PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 852Ile Thr Tyr Ser Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser1 5 10 15Gly Gly Ala Tyr Asp Ile Ile Ile Cys Asp Glu Cys His Ser20 25 3085337PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 853Ala Arg Ala Leu Ala His Gly Val Arg Val Leu Glu Asp Gly Val Asn1 5 10 15Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser Phe Ser Ile Phe Leu Leu20 25 30Ala Leu Leu Ser Cys3585436PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 854Asp Pro Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Leu1 5 10 15Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala20 25 30Pro Leu Gly Gly3585536PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 855Asp Pro Arg His Arg Ser Arg Asn Val Gly Lys Val Ile Asp Thr Leu1 5 10 15Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Val Val Gly Ala20 25 30Pro Leu Gly Gly3585632PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 856Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe1 5 10 15Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His Arg Leu20 25 3085732PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 857Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr1 5 10 15Thr Ile Phe Lys Ile Arg Met Tyr Val Gly Gly Val Glu His Arg Leu20 25 3085828PRTArtificial Sequencemodified_res(1)xaa = can be any naturally occurring amino acid 858Xaa Gly Gly Arg Lys Pro Ala Arg Leu Ile Val Phe Pro Asp Leu Gly1 5 10 15Val Arg Val Cys Glu Lys Met Ala Leu Tyr Asp Val20 2585928PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 859Lys Gly Gly Lys Lys Ala Ala Arg Leu Ile Val Tyr Pro Asp Leu Gly1 5 10 15Val Arg Val Cys Glu Lys Met Ala Leu Tyr Asp Val20 2586023PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 860Ile Gln Leu Ile Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala1 5 10 15Leu Asn Cys Asn Asp Ser Leu2086123PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 861Ile Gln Leu Val Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala1 5 10 15Leu Asn Cys Asn Asp Ser Leu2086223PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 862Leu Pro Ala Leu Ser Thr Gly Leu Ile His Leu His Gln Asn Ile Val1 5 10 15Asp Val Gln Tyr Leu Tyr Gly2086315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 863Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys1 5 10 1586415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 864Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp1 5 10 1586515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 865Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Ser Leu1 5 10 1586615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 866Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser1 5 10 1586715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 867Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val1 5 10 1586815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 868Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu1 5 10 1586915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 869Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu Arg Ala1 5 10 1587015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 870Ala Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val1 5 10 1587115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 871Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu1 5 10 1587215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 872Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly1 5 10 1587315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 873Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Ala1 5 10 1587415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 874Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Ala1 5 10 1587515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 875Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala1 5

10 1587615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 876Thr Arg Val Pro Tyr Phe Val Arg Ala Gln Gly Leu Ile Arg Ala1 5 10 1587715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 877Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Leu Gly Cys Ile Ile1 5 10 1587815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 878Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Leu Gly Cys Ile Val1 5 10 1587919PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 879Pro Glu Tyr Asp Glu Leu Glu Leu Ile Thr Ser Cys Ser Ser Asn Val1 5 10 15Ser Val Ala88020PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 880Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Ser Pro Val Val Val Gly1 5 10 15Thr Thr Asp Arg2088119PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 881Gly Trp Ala Gly Trp Leu Leu Ser Pro Arg Gly Ser Pro Arg Pro Ser1 5 10 15Trp Gly Pro88218PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 882Val Val Cys Cys Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr1 5 10 15Pro Cys88317PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 883Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Val Cys Ala Cys Leu Trp1 5 10 15Met88415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 884Gly Val Leu Phe Gly Leu Ala Tyr Phe Ser Met Val Gly Asn Trp1 5 10 1588521PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 885Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Ala Arg Ala Gln Ala Pro1 5 10 15Pro Pro Ser Trp Asp2088615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 886Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val1 5 10 1588715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 887Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala1 5 10 1588815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 888Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe1 5 10 1588915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 889Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys1 5 10 1589015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 890Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Lys Phe Ile1 5 10 1589115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 891Glu Thr Ala Gly Val Arg Leu Thr Val Leu Ala Thr Ala Thr Thr1 5 10 1589215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 892Ala Gly Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro Pro Gly1 5 10 1589315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 893Val Arg Leu Thr Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Val1 5 10 1589415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 894Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys Ile Met Ser Gly1 5 10 1589515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 895Val Asn Leu Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Val Val1 5 10 1589615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 896His Ala Gly Leu Arg Asp Leu Ala Val Ala Val Glu Pro Val Val1 5 10 1589715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 897Thr Thr Leu Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Ala Gln1 5 10 1589815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 898Val Met Gly Ser Ser Tyr Gly Phe Gln Tyr Ser Pro Gly Gln Arg1 5 10 1589917PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 899Val Leu Thr Ser Met Leu Thr Asp Pro Ser His Ile Thr Ala Glu Thr1 5 10 15Ala90017PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 900Val Leu Thr Ser Met Leu Thr Asp Pro Ser His Ile Thr Ala Glu Ala1 5 10 15Ala90116PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 901Gly Glu Val Gln Val Val Ser Thr Ala Thr Gln Ser Phe Leu Ala Thr1 5 10 1590216PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 902Gly Glu Val Gln Val Leu Ser Thr Val Thr Gln Ser Phe Leu Gly Thr1 5 10 1590315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 903Ala Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val1 5 10 1590415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 904Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu1 5 10 1590521PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 905Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Ala Arg Ala Lys Ala Pro1 5 10 15Pro Pro Ser Trp Asp2090615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 906Gln Thr Val Asp Phe Ser Leu Asp Pro Thr Phe Thr Ile Glu Thr1 5 10 1590718PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 907Val Phe Thr Gly Leu Thr His Ile Asp Ala His Phe Leu Ser Gln Thr1 5 10 15Lys Gln90815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 908Gly Val Leu Ala Gly Leu Ala Tyr Tyr Ser Met Val Gly Asn Trp1 5 10 1590915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 909Tyr Tyr Leu Thr Arg Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala1 5 10 1591015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 910Ser Gly Lys Ser Thr Lys Val Pro Val Ala Tyr Ala Ala Gln Gly1 5 10 1591115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 911Lys Ser Thr Lys Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys1 5 10 1591215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 912Thr Lys Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu1 5 10 1591315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 913Val Pro Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu1 5 10 1591415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 914Val Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro1 5 10 1591515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 915Thr Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala1 5 10 1591615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 916Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Ala Gly Ala1 5 10 1591715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 917Ala Phe Cys Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Ser Val1 5 10 1591815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 918Ala Phe Cys Ser Ala Leu Tyr Val Gly Asp Leu Cys Gly Ser Val1 5 10 1591915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 919Pro Ala Leu Ser Thr Gly Leu Leu His Leu His Gln Asn Ile Val1 5 10 1592015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 920Ser Gly Met Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala1 5 10 1592115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 921Met Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala1 5 10 1592215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 922Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp1 5 10 1592315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 923Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp Tyr Glu1 5 10 1592415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 924Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Ile Met Ser1 5 10 1592515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 925Gly Val Ala Gly Ala Leu Val Ala Phe Lys Ile Met Ser Gly Glu1 5 10 1592615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 926Thr Thr Leu Leu Leu Asn Ile Leu Gly Gly Trp Leu Ala Ala Gln1 5 10 1592715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 927Ala Val Arg Thr Lys Leu Lys Leu Thr Pro Leu Pro Ala Ala Ser1 5 10 1592817PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 928Pro Met Gly Phe Ser Tyr Asp Thr Arg Cys Phe Asp Ser Thr Val Thr1 5 10 15Glu92916PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 929Asn Thr Pro Gly Leu Pro Val Cys Gln Asp His Leu Glu Phe Trp Glu1 5 10 1593019PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 930Leu Glu Asp Arg Asp Arg Ser Glu Leu Ser Pro Leu Leu Leu Ser Thr1 5 10 15Thr Glu Trp93120PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 931Thr Val Pro Gln Asp Ala Val Ser Arg Ser Gln Arg Arg Gly Arg Thr1 5 10 15Gly Arg Gly Arg2093216PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 932Phe Thr Glu Ala Met Thr Arg Tyr Ser Ala Pro Pro Gly Asp Pro Pro1 5 10 1593315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 933Leu Pro Gly Cys Ser Phe Ser Ile Phe Leu Leu Ala Leu Leu Ser1 5 10 1593415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 934Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser1 5 10 1593515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 935Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu1 5 10 1593615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 936Ile Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala1 5 10 1593715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 937Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys1 5 10 1593815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 938Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys Ile Met1 5 10 1593915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 939Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr1 5 10 1594015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 940Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg1 5 10 1594115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 941Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu Arg1 5 10 1594215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 942Gly Gln Gly Trp Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln1 5 10 1594315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 943Gly Cys Ile Val Val Ser Met Thr Gly Arg Asp Lys Thr Gln Val1 5 10 1594415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 944Ser Tyr Leu Lys Gly Ser Ser Gly Gly Pro Leu Leu Cys Pro Ser1 5 10 1594515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 945Thr Gly Glu Ile Pro Phe Tyr Gly Lys Ala Ile Pro Ile Glu Val1 5 10 1594615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 946Phe Phe Thr Trp Leu Asp Gly Val Gln Ile His Arg Tyr Ala Pro1 5 10 1594715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 947Asp Leu Pro Gln Ile Ile Glu Arg Leu His Gly Leu Ser Ala Phe1 5 10 1594815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 948Asp Leu Pro Gln Ile Ile Gln Arg Leu His Gly Leu Ser Ala Phe1 5 10 1594915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 949Gly Leu Pro Val Ser Ala Leu Arg Gly Arg Glu Ile Leu Leu Gly1 5 10 1595015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 950Cys Gly Tyr Arg Arg Cys Arg Ala Ser Gly Val Leu Thr Thr Ser1 5 10 1595116PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 951Asn Ala Val Ala Tyr Tyr Arg Gly Leu Asp Val Ser Val Ile Pro Thr1 5 10 1595215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 952Glu Phe Val Gln Asp Cys Asn Cys Ser Ile Tyr Pro Gly His Val1 5 10 1595315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 953Pro Thr Ser Gly Asp Val Val Val Val Ala Thr Asp Ala Leu Met1 5 10 1595415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 954Leu Trp Ala Arg Met Ile Leu Met Thr His Phe Phe Ser Ile Leu1 5 10 1595515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 955Leu Trp Val Arg Met Val Leu Met Thr His Phe Phe Ser Ile Leu1 5 10 1595615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 956Glu Thr Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro1 5 10 1595715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 957Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly1 5 10 1595815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 958Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Val1 5 10 1595918PRTArtificial SequenceDescription of Artificial Sequence

Synthetic Peptide 959Val Val Cys Cys Ser Met Ser Tyr Ser Trp Thr Gly Ala Leu Ile Thr1 5 10 15Pro Cys96015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 960Ala Ala Gly Leu Arg Asp Leu Ala Val Ala Val Glu Pro Ile Val1 5 10 1596115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 961Ala Val Arg Thr Lys Leu Lys Leu Thr Pro Ile Pro Ala Ala Ser1 5 10 1596213PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 962Leu Gly Lys Val Ile Asp Thr Leu Thr Cys Gly Phe Ala1 5 1096313PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 963Gly Lys Val Ile Asp Thr Leu Thr Cys Gly Phe Ala Asp1 5 1096415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 964Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu Val Gly1 5 10 1596515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 965Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala Pro1 5 10 1596615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 966Asp Leu Met Gly Tyr Ile Pro Val Val Gly Ala Pro Leu Gly Gly1 5 10 1596715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 967Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Val Val Gly Ala1 5 10 1596815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 968Phe Ala Asp Leu Met Gly Tyr Ile Pro Val Val Gly Ala Pro Leu1 5 10 1596915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 969Asp Leu Met Gly Tyr Ile Pro Val Val Gly Ala Pro Leu Gly Gly1 5 10 1597015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 970Leu Ala His Gly Val Arg Val Leu Glu Asp Gly Val Asn Tyr Ala1 5 10 1597115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 971His Gly Val Arg Val Leu Glu Asp Gly Val Asn Tyr Ala Thr Gly1 5 10 1597215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 972Val Arg Val Leu Glu Asp Gly Val Asn Tyr Ala Thr Gly Asn Leu1 5 10 1597315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 973Val Leu Glu Asp Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gly1 5 10 1597415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 974Glu Asp Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser1 5 10 1597515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 975Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala1 5 10 1597615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 976Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr1 5 10 1597715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 977Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr Leu Gly1 5 10 1597815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 978Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr Leu Gly Phe Gly1 5 10 1597915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 979Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala Ser Arg Gly1 5 10 1598015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 980Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr Leu1 5 10 1598115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 981Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly1 5 10 1598215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 982Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro1 5 10 1598315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 983Gln Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile1 5 10 1598415PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 984Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala Ser1 5 10 1598515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 985Gly His Ala Val Gly Ile Phe Arg Ala Ala Val Cys Thr Arg Gly1 5 10 1598616PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 986Thr Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Thr Cys Val Thr Gln1 5 10 1598716PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 987Thr Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Val Ala Val Thr Gln1 5 10 1598816PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 988Ser Gly His Arg Met Ala Trp Asp Met Met Met Asn Trp Ser Pro Thr1 5 10 1598916PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 989Thr Gly His Arg Met Ala Trp Asp Met Met Met Asn Trp Ser Pro Thr1 5 10 1599067PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 990Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn1 5 10 15Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gly Gly Gln Ile Val Gly20 25 30Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu Gly Val Arg Ala35 40 45Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg Gly Arg Arg Gln Pro50 55 60Ile Pro Lys6599156PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 991Val Asn Leu Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Val Val Gly1 5 10 15Val Val Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly Glu Gly20 25 30Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala Ser Arg Gly Asn35 40 45His Val Ser Pro Thr His Tyr Val50 5599220PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 992Ile Lys Gly Gly Arg His Leu Ile Phe Cys His Ser Lys Lys Lys Cys1 5 10 15Asp Glu Leu Ala2099321PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 993Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Ala Arg Ala Gln Ala Pro1 5 10 15Pro Pro Ser Trp Asp2099441PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 994Tyr Leu His Ala Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pro Val1 5 10 15Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val20 25 30Ala Ala Thr Leu Gly Phe Gly Ala Tyr35 4099537PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 995Gly Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile1 5 10 15Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys20 25 30Ile Met Ser Gly Glu3599637PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 996Gly Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile1 5 10 15Leu Ala Gly Tyr Gly Ala Gly Ile Ser Gly Ala Leu Val Ala Phe Lys20 25 30Ile Met Ser Gly Glu3599715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 997Cys Gly Tyr Arg Arg Cys Arg Ala Ser Gly Val Leu Thr Thr Ser1 5 10 1599815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 998Pro Val Asn Ser Trp Leu Gly Asn Ile Ile Met Tyr Ala Pro Thr1 5 10 1599915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 999Pro Val Asn Ser Trp Leu Gly Asn Ile Ile Gln Tyr Ala Pro Thr1 5 10 15100034PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1000Ser Gly Met Phe Asp Ser Ser Val Leu Cys Glu Cys Tyr Asp Ala Gly1 5 10 15Cys Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Arg Leu Arg20 25 30Ala Tyr100134PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1001Ser Gly Met Phe Asp Ser Val Val Leu Cys Glu Cys Tyr Asp Ala Gly1 5 10 15Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu Arg20 25 30Ala Tyr100234PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1002Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu1 5 10 15Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala Ser Leu Met20 25 30Ala Phe100316PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1003Gly Glu Val Gln Val Val Ser Thr Ala Thr Gln Ser Phe Leu Ala Thr1 5 10 15100416PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1004Gly Glu Val Gln Val Leu Ser Thr Val Thr Gln Ser Phe Leu Gly Thr1 5 10 15100516PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1005Phe Ser Asp Asn Ser Thr Pro Pro Ala Val Pro Gln Thr Tyr Gln Val1 5 10 15100656PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1006Val Asn Leu Leu Pro Gly Ile Leu Ser Pro Gly Ala Leu Val Val Gly1 5 10 15Val Ile Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro Gly Glu Gly20 25 30Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala Ser Arg Gly Asn35 40 45His Val Ala Pro Thr His Tyr Val50 55100734PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1007Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu1 5 10 15Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Val Ala Ser Met Met20 25 30Ala Phe100818PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1008Val Val Cys Cys Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr1 5 10 15Pro Cys100918PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1009Val Val Cys Cys Ser Met Ser Tyr Ser Trp Thr Gly Ala Leu Ile Thr1 5 10 15Pro Cys101019PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1010Leu Thr Pro Pro His Ser Ala Lys Ser Lys Phe Gly Tyr Gly Ala Lys1 5 10 15Asp Val Arg101119PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1011Leu Thr Pro Pro His Ser Ala Lys Ser Lys Tyr Gly Tyr Gly Ala Lys1 5 10 15Glu Val Arg101219PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1012Leu Thr Pro Pro His Ser Ala Arg Ser Lys Tyr Gly Tyr Gly Ala Lys1 5 10 15Glu Val Arg101316PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1013Thr Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Val Ala Val Thr Gln1 5 10 15101421PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1014Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Ala Arg Ala Lys Ala Pro1 5 10 15Pro Pro Ser Trp Asp20101519PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1015Leu Glu Asp Arg Asp Arg Ser Glu Leu Ser Pro Leu Leu Leu Ser Thr1 5 10 15Thr Glu Trp101619PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1016Leu Glu Asp Arg Asp Arg Ser Gln Leu Ser Pro Leu Leu His Ser Thr1 5 10 15Thr Glu Trp101718PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1017Pro Glu Tyr Asp Leu Glu Leu Ile Thr Ser Cys Ser Ser Asn Val Ser1 5 10 15Val Ala101820PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1018Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Ser Pro Val Val Val Gly1 5 10 15Thr Thr Asp Arg20101917PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1019Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Val Cys Ala Cys Leu Trp1 5 10 15Met102016PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1020Ser Gly His Arg Met Ala Trp Asp Met Met Met Asn Trp Ser Pro Thr1 5 10 15102116PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1021Thr Gly His Arg Met Ala Trp Asp Met Met Met Asn Trp Ser Pro Thr1 5 10 15102230PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1022Ile Thr Tyr Ser Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser1 5 10 15Gly Gly Ala Tyr Asp Ile Ile Ile Cys Asp Glu Cys His Ser20 25 30102337PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1023Ala Arg Ala Leu Ala His Gly Val Arg Val Leu Glu Asp Gly Val Asn1 5 10 15Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser Phe Ser Ile Phe Leu Leu20 25 30Ala Leu Leu Ser Cys35102436PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1024Asp Pro Arg His Arg Ser Arg Asn Val Gly Lys Val Ile Asp Thr Leu1 5 10 15Thr Cys Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Val Val Gly Ala20 25 30Pro Leu Gly Gly35102532PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1025Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe1 5 10 15Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His Arg Leu20 25 30102632PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1026Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr1 5 10 15Thr Ile Phe Lys Ile Arg Met Tyr Val Gly Gly Val Glu His Arg Leu20 25 30102728PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1027Lys Gly Gly Arg Lys Pro Ala Arg Leu Ile Val Phe Pro Asp Leu Gly1 5 10 15Val Arg Val Cys Glu Lys Met Ala Leu Tyr Asp Val20 25102828PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1028Lys Gly Gly Lys Lys Ala Ala Arg Leu Ile Val Tyr Pro Asp Leu Gly1 5 10 15Val Arg Val Cys Glu Lys Met Ala Leu Tyr Asp Val20 25102923PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1029Ile Gln Leu Ile Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala1 5 10 15Leu Asn Cys Asn Asp Ser Leu20103023PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1030Ile Gln Leu Val Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala1 5 10 15Leu Asn Cys Asn Asp Ser Leu20103123PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide

1031Leu Pro Ala Leu Ser Thr Gly Leu Ile His Leu His Gln Asn Ile Val1 5 10 15Asp Tyr Gln Tyr Leu Tyr Gly2010329PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1032Arg Pro Met Thr Tyr Lys Ala Ala Leu1 510339PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1033Leu Pro Cys Val Leu Trp Pro Val Leu1 5103420PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1034Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr1 5 10 15Leu Pro Gly Asn2010359PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1035His Met Trp Asn Phe Ile Ser Gly Ile1 5103620PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1036Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr Leu Pro1 5 10 15Gly Asn Pro Ala20103723PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1037His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser1 5 10 15Thr Leu Pro Gly Asn Pro Ala20103826PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1038Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala1 5 10 15Gly Val Ala Gly Ala Leu Val Ala Phe Lys20 25103916PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1039Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu Arg1 5 10 15104020PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1040Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr Thr1 5 10 15Ile Phe Lys Ile20104120PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1041Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe Thr1 5 10 15Ile Phe Lys Ile20104210PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1042Ala Tyr Ser Gln Gln Thr Arg Gly Leu Leu1 5 10104312PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1043Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Leu Gly1 5 10104413PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1044Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr Pro1 5 10104510PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1045Ser Pro Gly Ala Leu Val Val Gly Val Ile1 5 1010468PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1046Leu Pro Arg Arg Gly Pro Arg Leu1 5104719PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1047Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn Arg Arg1 5 10 15Pro Gln Asp104811PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1048Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn Arg1 5 1010499PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1049Gln Arg Lys Thr Lys Arg Asn Thr Asn1 510508PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1050Gln Arg Lys Thr Lys Arg Asn Thr1 510519PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1051Arg Lys Thr Lys Arg Asn Thr Asn Arg1 5105221PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1052Lys Gly Gly Arg Lys Pro Ala Arg Leu Ile Val Phe Pro Asp Leu Gly1 5 10 15Val Arg Val Cys Glu2010539PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1053Ala Arg Leu Ile Val Phe Pro Asp Leu1 5105426PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1054Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala1 5 10 15Gly Val Ala Gly Ala Leu Val Ala Phe Lys20 25105515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1055Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly1 5 10 15105615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1056Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly1 5 10 15105715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1057Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly1 5 10 15105815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1058Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala1 5 10 15105915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1059Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val1 5 10 15106015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1060Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe1 5 10 15106116PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1061Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu Arg1 5 10 15106215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1062Ala Gly Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val1 5 10 15106315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1063Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu1 5 10 15106412PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1064Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Leu Gly1 5 10106515PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1065Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Leu Gly Cys Ile Val1 5 10 15106613PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1066Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr Pro1 5 10106718PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1067Val Val Cys Cys Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr1 5 10 15Pro Cys106832PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1068Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe1 5 10 15Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His Arg Leu20 25 30106915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1069Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe1 5 10 15107015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1070Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe Thr1 5 10 15107115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1071Leu Trp His Tyr Pro Cys Thr Val Asn Phe Thr Ile Phe Lys Val1 5 10 15107215PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1072Thr Val Asn Phe Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly1 5 10 15107315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1073Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His Arg1 5 10 15107432PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1074Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr1 5 10 15Thr Ile Phe Lys Ile Arg Met Tyr Val Gly Gly Val Glu His Arg Leu20 25 30107520PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1075Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr Thr1 5 10 15Ile Phe Lys Ile20107615PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1076Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr1 5 10 15107715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1077Leu Trp His Tyr Pro Cys Thr Val Asn Tyr Thr Ile Phe Lys Ile1 5 10 15107815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1078Thr Val Asn Tyr Thr Ile Phe Lys Ile Arg Met Tyr Val Gly Gly1 5 10 15107915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1079Thr Ile Phe Lys Ile Arg Met Tyr Val Gly Gly Val Glu His Arg1 5 10 15108011PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1080Arg Met Tyr Val Gly Gly Val Glu His Arg Leu1 5 10108123PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1081His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser1 5 10 15Thr Leu Pro Gly Asn Pro Ala20108220PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1082Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr Leu Pro1 5 10 15Gly Asn Pro Ala20108320PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1083Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr1 5 10 15Leu Pro Gly Asn20108429PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1084Lys Phe Pro Gly Gly Gly Gln Ile Val Gly Gly Val Tyr Leu Leu Pro1 5 10 15Arg Arg Gly Pro Arg Leu Gly Val Arg Ala Thr Arg Lys20 25108522PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1085Lys Phe Pro Gly Gly Gly Gln Ile Val Gly Gly Val Tyr Leu Leu Pro1 5 10 15Arg Arg Gly Pro Arg Leu20108610PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1086Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu1 5 1010878PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1087Leu Pro Arg Arg Gly Pro Arg Leu1 510889PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1088Gly Pro Arg Leu Gly Val Arg Ala Thr1 510899PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1089Arg Leu Gly Val Arg Ala Thr Arg Lys1 5109014PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1090Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr1 5 10109110PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1091Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu1 5 10109219PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1092Ala Tyr Ala Ala Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Ser Val1 5 10 15Ala Ala Thr10939PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1093Asp Leu Met Gly Tyr Ile Pro Ala Val1 5109410PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1094Gly Tyr Ile Pro Leu Val Gly Ala Pro Leu1 5 10109513PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1095Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala Pro Leu1 5 1010969PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1096Cys Ile Asn Gly Val Cys Trp Thr Val1 5109716PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1097Gly Glu Val Gln Val Val Ser Thr Ala Thr Gln Ser Phe Leu Ala Thr1 5 10 15109825PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1098Gly Glu Val Gln Val Val Ser Thr Ala Thr Gln Ser Phe Leu Ala Thr1 5 10 15Cys Ile Asn Gly Val Cys Trp Thr Val20 25109923PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1099His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser1 5 10 15Thr Leu Pro Gly Asn Pro Ala20110020PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1100Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr1 5 10 15Leu Pro Gly Asn20110120PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1101Asn Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Leu Ser Thr Leu Pro1 5 10 15Gly Asn Pro Ala2011029PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1102Gln Tyr Leu Ala Gly Leu Ser Thr Leu1 511039PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1103His Met Trp Asn Phe Ile Ser Gly Ile1 5110432PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1104Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe1 5 10 15Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His Arg Leu20 25 30110520PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1105Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe Thr1 5 10 15Ile Phe Lys Ile20110620PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1106Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe Thr1 5 10 15Ile Phe Lys Val20110732PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1107Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr1 5 10 15Thr Ile Phe Lys Ile Arg Met Tyr Val Gly Gly Val Glu His Arg Leu20 25 30110820PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1108Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Tyr Thr1 5 10 15Ile Phe Lys Ile2011099PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1109Asp Tyr Pro Tyr Arg Leu Trp His Tyr1 511109PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1110Thr Val Asn Tyr Thr Ile Phe Lys Ile1 511118PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1111Thr Ile Asn Tyr Thr Ile Phe Lys1 511129PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1112Thr Val Asn Phe Thr Ile Phe Lys Val1 5111310PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1113His Tyr Pro Cys Thr Val Asn Tyr Thr Ile1 5 10111410PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1114His Tyr Pro Cys Thr Val Asn Phe Thr Ile1 5 10111510PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1115Arg Met Tyr Val Gly Gly Val Glu His Arg1 5 10111616PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1116Ala Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Thr Val Arg Leu Arg1 5 10 1511179PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1117Thr Pro Ala Glu Thr Thr Val Arg Leu1 5111823PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1118Gly Trp Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln Gln Thr Arg1 5 10 15Gly Leu Leu Gly Cys Ile Val20111915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1119Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Leu

Gly Cys Ile Val1 5 10 15112012PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1120Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Leu Gly1 5 10112115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1121Gly Gln Gly Trp Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln1 5 10 1511229PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1122Arg Leu Leu Ala Pro Ile Thr Ala Tyr1 5112325PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1123Gly Gln Gly Trp Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln Gln1 5 10 15Thr Arg Gly Leu Leu Gly Cys Ile Val20 25112422PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1124Gly Gln Gly Trp Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln Gln1 5 10 15Thr Arg Gly Leu Leu Gly20112510PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1125Ala Tyr Ser Gln Gln Thr Arg Gly Leu Leu1 5 1011269PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1126Ala Tyr Ser Gln Gln Thr Arg Gly Leu1 5112726PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1127Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala1 5 10 15Gly Val Ala Gly Ala Leu Val Ala Phe Lys20 2511289PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1128Ile Leu Ala Gly Tyr Gly Ala Gly Val1 511299PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1129Val Ala Gly Ala Leu Val Ala Phe Lys1 5113010PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1130Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu1 5 10113118PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1131Val Val Cys Cys Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr1 5 10 15Pro Cys113213PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1132Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr Pro1 5 10113310PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1133Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu1 5 1011349PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1134Ser Tyr Thr Trp Thr Gly Ala Leu Ile1 5113516PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1135Phe Thr Asp Asn Ser Ser Pro Pro Ala Val Pro Gln Thr Phe Gln Val1 5 10 15113619PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1136Leu Glu Asp Arg Asp Arg Ser Glu Leu Ser Pro Leu Leu Leu Ser Thr1 5 10 15Thr Glu Trp113716PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1137Leu Glu Asp Arg Asp Arg Ser Glu Leu Ser Pro Leu Leu Leu Ser Thr1 5 10 1511389PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1138Arg Ser Glu Leu Ser Pro Leu Leu Leu1 511399PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1139Glu Leu Ser Pro Leu Leu Leu Ser Thr1 5114010PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1140Asp Arg Asp Arg Ser Glu Leu Ser Pro Leu1 5 1011419PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1141Leu Glu Asp Arg Asp Arg Ser Glu Leu1 511429PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1142Leu Glu Asp Arg Asp Arg Ser Glu Leu1 5114321PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1143Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Ala Arg Ala Gln Ala Pro1 5 10 15Pro Pro Ser Trp Asp2011449PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1144Tyr Leu Val Ala Tyr Gln Ala Thr Val1 5114517PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1145Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn1 5 10 15Arg114611PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1146Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn Arg1 5 1011479PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1147Gln Arg Lys Thr Lys Arg Asn Thr Asn1 511489PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1148Arg Lys Thr Lys Arg Asn Thr Asn Arg1 511499PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1149Met Ser Thr Asn Pro Lys Pro Gln Arg1 511509PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1150Met Ser Thr Asn Pro Lys Pro Gln Lys1 5115121PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1151Leu Ile Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn1 5 10 15Cys Asn Asp Ser Leu20115217PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1152Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Ser1 5 10 15Leu115310PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1153Leu Ile Asn Thr Asn Gly Ser Trp His Ile1 5 10115410PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1154Arg Thr Ala Leu Asn Cys Asn Asp Ser Leu1 5 10115516PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1155Leu Ile Asn Thr Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn1 5 10 15115610PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1156Ser Trp His Ile Asn Arg Thr Ala Leu Asn1 5 10115715PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1157Thr Thr Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr1 5 10 1511589PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1158Thr Thr Ile Leu Gly Ile Gly Thr Val1 511599PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1159Thr Ile Leu Gly Ile Gly Thr Val Leu1 5116018PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1160Phe Asp Ser Ser Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp1 5 10 15Tyr Glu116115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1161Phe Asp Ser Ser Val Leu Cys Glu Cys Tyr Asp Ala Gly Cys Ala1 5 10 15116210PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1162Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala1 5 10116315PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1163Val Val Leu Cys Glu Cys Tyr Asp Ala Gly Ala Ala Trp Tyr Glu1 5 10 15116420PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1164Ala Arg Leu Ile Val Phe Pro Asp Leu Gly Val Arg Val Cys Glu Lys1 5 10 15Met Ala Leu Tyr2011659PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1165Ala Arg Leu Ile Val Phe Pro Asp Leu1 5116610PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1166Arg Leu Ile Val Phe Pro Asp Leu Gly Val1 5 1011679PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1167Arg Val Cys Glu Lys Met Ala Leu Tyr1 5116815PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1168Ala Phe Cys Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Ser Val1 5 10 15116915PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1169Gly Val Leu Phe Gly Leu Ala Tyr Phe Ser Met Val Gly Asn Trp1 5 10 15117015PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1170Thr Arg Val Pro Tyr Phe Val Arg Ala Gln Gly Leu Ile Arg Ala1 5 10 15117115PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1171Thr Thr Leu Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Ala Gln1 5 10 15117210PRTArtificial SequenceDescription of Artificial Sequence Synthetic Peptide 1172Leu Leu Phe Asn Ile Leu Gly Gly Trp Val1 5 10

Claims

1. An immunogenic composition comprising a pharmaceutically acceptable carrier and one or more epitopes from polypeptides A120-A124, B25-B30, B46-B48, B84-B92, C106, C113-C114, 1627, 1628, 1629, 1604, 1630, C97, 1547, B94-B98, A272-A276, B120, B122, C108, C134, C152, 1606, 1607, 1577, 1578, B50-52, 1623, C130, 1603, C96, C191, A216-A224, A242-A244, C92-C93, A174, B32-B38, B100-B102, C135, C162, 1618, 1622, 1624, 1546, 1556, A114, B58, B112-B118, B18-B22, C112, C116, C122, C127, C144, C159-C160, C174, 1558, 1581, C95, C129, C157-C158, A254-A258, 1605, C109, C161, 1547, 1555, 1558, 1559, 1560, 1563, 1592, 1605, 1616, 1621, 1623, 1625, 1649, 1650, 1651, 1652, 1654, 1655, 1656, 1545, 1552, 1557, 1615, 1617, 1631, 1632, 1641, 1647, 1653, A141, C114, C134, C135, 1426, 1506, 1526, 1553, 1562, 1565, 1580, 1587, 1624, 1627, 1843, or 1838, wherein the immunogenic composition stimulates a specific T cell response to hepatitis C virus when administered to a subject in an effective amount.

2. The immunogenic composition of claim 1, wherein the epitope further comprises 1 to 30 naturally occurring amino acid residues at its N-terminus, its C-terminus or at its N- and C-terminus.

3. The immunogenic composition of claim 1, wherein the epitope further comprises 2 to 10 naturally occurring amino acid residues at its N-terminus, its C-terminus or at its N- and C-terminus.

4. The immunogenic composition of claim 1, wherein the epitope further comprises 2 to 6 naturally occurring amino acid residues at its N-terminus, its C-terminus or at its N- and C-terminus.

5. The immunogenic composition of claim 1, wherein the epitope further comprises 2 to 100 non-naturally occurring amino acid residues at its N-terminus, its C-terminus or at its N- and C-terminus.

6. The immunogenic composition of claim 1, wherein the epitope further comprises 2 to 20 non-naturally occurring amino acid residues at its N-terminus, its C-terminus or at its N- and C-terminus.

7. The immunogenic composition of claim 1, wherein the epitope further comprises 1 to 1000 non-naturally occurring amino acid residues at its N-terminus, its C-terminus or at its N- and C-terminus.

8. The immunogenic composition of claim 1, wherein at least one of the epitopes is an HLA A0201 binding epitope from polypeptide 1545, 1552, 1555, 1558, 1559, 1560, 1577, 1592, 1604, 1605, 1615, 1617, 1621, 1627, 1631, 1632, 1641, 1647, 1650, 1651, 1652, 1653, 1654, or 1655.

9. The immunogenic composition of claim 1, wherein at least one of the epitopes is an HLA-B*0702 binding epitope from polypeptide 1506, 1526, 1547, 1552, 1553, 1555, 1558, 1562, 1563, 1565, 1577, 1578, 1580, 1587, 1592, 1604, 1605, 1621, 1623, 1624, 1627, 1628, 1647, 1650, 1651, 1843 or 1838.

10. The immunogenic composition of claim 1, further comprising an immunomodulating substance.

11. The immunogenic composition of claim 1, wherein the immuno-modulating substance is a polycationic polypeptide, an immunomodulating nucleic acid, or mixtures thereof.

12. The immunogenic composition of claim 1, wherein immunomodulating nucleic acid is a deoxyinosine and/or deoxyuracil containing oligodeoxynucleotide.

13. The immunogenic composition of claim 1, wherein the epitope is provided in a dendritic cell pulsed with a protein, peptide, or RNA or transfected with a DNA comprising the epitope.

14. A method for stimulating a specific immune response against hepatitis C virus (HCV) in a subject comprising administering to the subject an effective amount of an immunogenic composition comprising one or more epitopes from polypeptides A120-A124, B25-B30, B46-B48, B84-B92, C106, C113-C114, 1627, 1628, 1629, 1604, 1630, C97, 1547, B94-B98, A272-A276, B120, B122, C108, C134, C152, 1606, 1607, 1577, 1578, B50-52, 1623, C130, 1603, C96, C191, A216-A224, A242-A244, C92-C93, A174, B32-B38, B100-B102, C135, C162, 1618, 1622, 1624, 1546, 1556, A114, B58, B112-B118, B18-B22, C112, C116, C122, C127, C144, C159-C160, C174, 1558, 1581, C95, C129, C157-C158, A254-A258, 1605, C109, C161, 1547, 1555, 1558, 1559, 1560, 1563, 1592, 1605, 1616, 1621, 1623, 1625, 1649, 1650, 1651, 1652, 1654, 1655, 1656, 1545, 1552, 1557, 1615, 1617, 1631, 1632, 1641, 1647, 1653, A141, C114, C134, C135, 1426, 1506, 1526, 1553, 1562, 1565, 1580, 1587, 1624, 1627, 1843, or 1838, wherein the specific immune response to hepatitis C virus is stimulated in the subject.

15. The method of claim 14, wherein the immunogenic composition further comprising an immunomodulating substance.

16. The method of claim 15, wherein the immunomodulating substance is a polycationic polypeptide, an immunomodulating nucleic acid, or mixtures thereof.

17. The method of claim 16, wherein immunomodulating nucleic acid is a deoxyinosine and/or deoxyuracile containing oligodeoxynucleotide.

18. The method of claim 14, wherein the epitope is provided in a dendritic cell pulsed with a protein, peptide, or RNA or transfected with a DNA comprising the epitope.

19. The method of claim 14, wherein at least one of the epitopes is an HLA A0201 binding epitope from polypeptide 1545, 1552, 1555, 1558, 1559, 1560, 1577, 1592, 1604, 1605, 1615, 1617, 1621, 1627, 1631, 1632, 1641, 1647, 1650, 1651, 1652, 1653, 1654, or 1655.

20. The method of claim 14, wherein at least one of the epitopes is an HLA-B*0702 binding epitope from polypeptide 1506, 1526, 1547, 1552, 1553, 1555, 1558, 1562, 1563, 1565, 1577, 1578, 1580, 1587, 1592, 1604, 1605, 1621, 1623, 1624, 1627, 1628, 1647, 1650, 1651, 1843 or 1838.

21. An isolated T cell that specifically recognizes an epitope of polypeptide A120-A124, B25-B30, B46-B48, B84-B92, C106, C113-C114, 1627, 1628, 1629, 1604, 1630, C97, 1547, B94-B98, A272-A276, B120, B122, C108, C134, C152, 1606, 1607, 1577, 1578, B50-52, 1623, C130, 1603, C96, C191, A216-A224, A242-A244, C92-C93, A174, B32-B38, B100-B102, C135, C162, 1618, 1622, 1624, 1546, 1556, A114, B58, B112-B118, B18-B22, C112, C116, C122, C127, C144, C159-C160, C174, 1558, 1581, C95, C129, C157-C158, A254-A258, 1605, C109, C161, 1547, 1555, 1558, 1559, 1560, 1563, 1592, 1605, 1616, 1621, 1623, 1625, 1649, 1650, 1651, 1652, 1654, 1655, 1656, 1545, 1552, 1557, 1615, 1617, 1631, 1632, 1641, 1647, 1653, A141, C114, C134, C135, 1426, 1506, 1526, 1553, 1562, 1565, 1580, 1587, 1624, 1627, 1843, or 1838.

22. A method of treating a hepatitis C virus infection in a subject comprising administering to the subject an effective amount of a composition comprising a T cell that specifically recognizes an epitope of polypeptide A120-A124, B25-B30, B46-B48, B84-B92, C106, C113-C114, 1627, 1628, 1629, 1604, 1630, C97, 1547, B94-B98, A272-A276, B120, B122, C108, C134, C152, 1606, 1607, 1577, 1578, B50-52, 1623, C130, 1603, C96, C191, A216-A224, A242-A244, C92-C93, A174, B32-B38, B100-B102, C135, C162, 1618, 1622, 1624, 1546, 1556, A114, B58, B112-B118, B18-B22, C112, C116, C122, C127, C144, C159-C160, C174, 1558, 1581, C95, C129, C157-C158, A254-A258, 1605, C109, C161, 1547, 1555, 1558, 1559, 1560, 1563, 1592, 1605, 1616, 1621, 1623, 1625, 1649, 1650, 1651, 1652, 1654, 1655, 1656, 1545, 1552, 1557, 1615, 1617, 1631, 1632, 1641, 1647, 1653, A141, C114, C134, C135, 1426, 1545, 1552, 1555, 1558, 1559, 1560, 1577, 1592, 1604, 1605, 1615, 1617, 1621, 1627, 1631, 1632, 1641, 1647, 1650, 1651, 1652, 1653, 1654, 1655, 1506, 1526, 1552, 1553, 1562, 1565, 1577, 1578, 1580, 1587, 1623, 1624, 1628, 1843, or 1838, wherein the hepatitis C virus infection is treated in the subject.

23. A method of stimulating an HLA-B*08 specific immune response against a hepatitis C virus in a subject comprising administering to the subject an effective amount of a composition comprising one or more epitopes of peptide sequences QRKTKRNTN (SEQ ID NO: 167), QRKTKRNT (SEQ ID NO: 166), SAKSKFGYG (SEQ ID NO: 193), SAKSKYGYG (SEQ ID NO: 194), or SARSKYGYG (SEQ ID NO: 195), wherein the HLA-B*08 specific immune response against the hepatitis C virus is stimulated in the subject.

24. A method of stimulating an HLA-B*2705 specific immune response against a hepatitis C virus in a subject comprising administering to the subject an effective amount of a composition comprising a peptide having sequence RKTKRNTNR (SEQ ID NO: 170), wherein the HLA-B*2705 specific immune response against the hepatitis C virus in the subject.

25. A method of stimulating an HLA-B*2705 and HLA-B*2709 specific immune responses against a hepatitis C virus in a subject comprising administering to the subject an effective amount of a composition comprising a peptide having sequence ARLIVFPDL (SEQ ID NO: 1053), wherein the HLA-B*2705 and HLA-B*2709 specific immune responses against the hepatitis C virus in the subject.

26. A method for stimulating a specific immune response against hepatitis C virus (HCV) in a subject comprising administering to the subject an effective amount of an immunogenic composition comprising one or more epitopes from polypeptides 1835, 84EX, 87EX, 89EX, 1426, 1650, 1836, 1846, 1651, 1800, 1799, C114, 1827, C112, C114EX, 1827EX, 1798, 1604, 1829, 1579, 1624, 1848, 1547, A1A7, A122EX, A122, 1825, A241, B8B38, C70EX, C92, C97, C106, or C134, wherein the specific immune response against the hepatitis C virus (HCV) is stimulated in the subject.