Patent Publication Number: US-2015087809-A1

Title: Hla-binding peptides, precursors thereof, dna fragments and recombinant vectors that code for those peptide sequences

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This is a divisional application based upon U.S. patent application Ser. No. 12/903,000, filed Oct. 12, 2010, which is a divisional of U.S. patent application Ser. No. 11/587,973, filed Oct. 30, 2006, which is a 371 National Stage of PCT Application No. PCT/JP2005/007231, filed Apr. 14, 2005, claiming priority based on Japanese Patent Application Nos. 2005-050164 filed Feb. 25, 2005, 2004-272314 filed Sep. 17, 2004 and 2004-135652 filed Apr. 30, 2004, the contents of all of which are incorporated herein by reference in their entirety. 
    
    
     TECHNICAL FIELD 
     The present invention relates to HLA-binding peptides, precursor thereof and DNA fragments and recombinant vectors coding for those sequences. 
     BACKGROUND ART 
     When one is infected with a virus such as hepatitis C virus (HCV) a virus specific immune response is induced to eliminate the virus following a defense by the innate immune system. 
     When a specific immune response is induced isolated viral particles lose their infectivity by neutralizing antibodies and are subsequently eliminated. In the other words, virus infected cells are lysed by cytotoxic T lymphocytes (CTLs). CTL recognizes as antigen an epitope peptide presented by an HLA class I molecule. Such epitope peptides are 8 to 11 amino acids in length. Therefore, it is critical to identify viral epitope peptides in order to develop a therapeutic vaccine against the virus. 
     A technique of this kind is known from Patent Publication 1. Patent Publication 1 states that an oligopeptide formed from a specific amino acid sequence has the property of binding to an HLA. 
     [Patent Publication 1] Japanese Patent Application Laid-open No. H8-151396 (1996) 
     DISCLOSURE OF THE INVENTION 
     However, the conventional technique described in the above-mentioned publication has room for improvement on the following points. 
     Firstly, it is unclear whether or not the HLA-binding peptide of the above-mentioned publication binds to an HLA molecule effectively, and there is still room for improvement in terms of the property of binding to an HLA. 
     Secondly, it is stated that the HLA-binding peptide of the above-mentioned publication has the property of binding to HLA-DQ4. However, it is unclear whether or not it binds to an HLA-A2 type molecule (product of the HLA-A*0201 gene and the like), which is often seen in European and American people, and an HLA-A24 type molecule (product of the HLA-A*2402 gene and the like), which is often seen in Japanese people. 
     The present invention has been accomplished under the above-mentioned circumstances, and provides HLA-binding peptides that exhibit high-affinity binding to a specific type of HLA molecule. 
     According to the present invention, there is provided an HLA-binding peptide binding to an HLA-A type molecule, the HLA-binding peptide containing at least one type of amino acid sequence selected from the group consisting of SEQ ID NOS: 1 to 183, and consisting of not less than 8 and not more than 11 amino acid residues. 
     Furthermore, according to the present invention, there is provided the HLA-binding peptide comprising at least one type of amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 2, 3, 5, 8, 12, 13, 14, 16, 17, 18, 19, 22, 23, 25, 27, 34, 37, 38, 40, 42, 45, 48, 49, 52, 53, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 65, 67, 71, 72, 74, 75, 76, 84, 86, 87, 90, 91, 92, 93, 94, 96, 97, 98, 100, 101, 102, 104, 106, 107, 108, 109, 110, 112, 123, 124, 126, 127, 131, 132, 133, 134, 135, 136, 137, 139, 141, 142, 146, 147, 149, 150, 152, 162, 170, 173, 176, 177, and 179. 
     Moreover, according to the present invention, there is provided an HLA-binding peptide binding to an HLA-A type molecule, the HLA-binding peptide containing an amino acid sequence formed by deletion, substitution, or addition of one or two amino acid residues of the amino acid sequence contained in the above-mentioned HLA-binding peptide, and consisting of not less than 8 and not more than 11 amino acid residues. 
     In this way, the construct containing an amino acid sequence formed by deletion, substitution, or addition of one or a few amino acid residues of a specific amino acid sequence that has the property of binding to an HLA-A type molecule can also exhibit the similar effect to that of the above-mentioned HLA-binding peptide. 
     Furthermore, according to the present invention, there is provided a DNA segment containing a DNA sequence coding for the above-mentioned HLA-binding peptide. 
     Moreover, according to the present invention, there is provided a recombinant vector containing a DNA sequence coding for the above-mentioned HLA-binding peptide. 
     Furthermore, according to the present invention, there is provided an HLA-binding peptide precursor changing within a mammalian body into the above-mentioned HLA-binding peptide. 
     In accordance with the present invention, since it includes a specific amino acid sequence, an HLA-binding peptide that has excellent properties in binding to an HLA-A type molecule can be obtained. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The above-mentioned object, other objects, features, and advantages will become more apparent from preferred embodiments explained below by reference to the attached drawing. 
         FIG. 1  A schematic drawing for explaining an active learning experiment design used in an embodiment. 
     
    
    
     BEST MODE FOR CARRYING OUT THE INVENTION 
     Modes for carrying out the present invention are explained below by reference to a drawing. In all the drawings, the same constitutional elements are denoted by the same reference numerals and symbols, so that the explanation will not be repeated. 
     Embodiment 1 
     In this embodiment a peptide that contains an amino acid sequence for which the binding to an HLA molecule, predicted by a hypothesis obtained using an active learning experiment method (Japanese Patent Application Laid-open No. H11-316754 (1999)), is 3 or greater in terms of a −log Kd value, and consists of not less than 8 and not more than 11 amino acid residues is used as a candidate for an HLA-binding peptide. As a result of a binding experiment, it has been confirmed that these peptides are actually HLA-binding peptides. 
     As a result, a large number of HLA-binding peptides that have excellent properties in binding to an HLA-A type molecule because they contain an amino acid sequence for which the binding to the HLA molecule in terms of a −log Kd value is 3 or greater could be obtained efficiently. 
     Specifically, the HLA-binding peptide related to this embodiment is an HLA-binding peptide that binds to an HLA-A type molecule, and that contains at least one type of amino acid sequence selected from the group consisting of SEQ ID NOS: 1 to 183, which will be described later, and that consists of not less than 8 and not more than 11 amino acid residues. 
     Among human HLA-A types, about 50% of Japanese people have the HLA-A24 type. For European and American people such as German people have the HLA-A2 type. 
     All of these sequences herein mentioned are sequences consisting of 9 amino acid residues contained in a certain genome protein of HCV (hepatitis C virus). 
     The sequences of SEQ ID NOS: 1 to 44 are given in Table 1 below. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 HLA-A24-BINDING PEPTIDE 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 SEQ 
                 D90208 
                   
                   
                 BINDING 
               
               
                   
                 ID 
                 PREDICTED 
                 PRE- 
                 SEQ 
                 EXPERIMENT 
               
               
                   
                 NO 
                 SCORE 
                 DICTED 
                 NAME 
                 DATA 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 1 
                 ILPCSFTTL 
                 6.9039 
                 674 
                 7.6571 
               
               
                   
                   
               
               
                   
                 2 
                 VILDSFDPI 
                 6.293 
                 2251 
                 5.32417 
               
               
                   
                   
               
               
                   
                 3 
                 RYAPVCKPL 
                 6.2755 
                 2132 
                 6.14848 
               
               
                   
                   
               
               
                   
                 4 
                 FWAKHMWNF 
                 6.0822 
                 1760 
                   
               
               
                   
                   
               
               
                   
                 5 
                 ALYDVVSTL 
                 6.0484 
                 2593 
                 6.38942 
               
               
                   
                   
               
               
                   
                 6 
                 TVLSDFKTW 
                 6.0021 
                 1986 
                   
               
               
                   
                   
               
               
                   
                 7 
                 PYIEQGMQL 
                 5.9628 
                 1716 
                   
               
               
                   
                   
               
               
                   
                 8 
                 WHYPCTVNF 
                 5.921 
                 616 
                 6.38729 
               
               
                   
                   
               
               
                   
                 9 
                 KFPPALPIW 
                 5.8662 
                 2280 
                   
               
               
                   
                   
               
               
                   
                 10 
                 TYSTYCKFL 
                 5.8658 
                 1292 
                   
               
               
                   
                   
               
               
                   
                 11 
                 AYSQQTRGL 
                 5.831 
                 1031 
                   
               
               
                   
                   
               
               
                   
                 12 
                 AQPGYPWPL 
                 5.8258 
                 77 
                 5.36419 
               
               
                   
                   
               
               
                   
                 13 
                 ILMTHFFSI 
                 5.8071 
                 2843 
                 7.89519 
               
               
                   
                   
               
               
                   
                 14 
                 SYTWTGALI 
                 5.8059 
                 2422 
                 7.12954 
               
               
                   
                   
               
               
                   
                 15 
                 SPPAVPQTF 
                 5.7982 
                 1215 
                   
               
               
                   
                   
               
               
                   
                 16 
                 LLPRRGPRL 
                 5.7503 
                 36 
                 7.71195 
               
               
                   
                   
               
               
                   
                 17 
                 ALYGVWPLL 
                 5.7447 
                 789 
                 6.98038 
               
               
                   
                   
               
               
                   
                 18 
                 LMTHFFSIL 
                 5.7443 
                 2844 
                 5.9169 
               
               
                   
                   
               
               
                   
                 19 
                 LLKRLHQWI 
                 5.7425 
                 1956 
                 6.857254 
               
               
                   
                   
               
               
                   
                 20 
                 YILLLFLLL 
                 5.738 
                 718 
                   
               
               
                   
                   
               
               
                   
                 21 
                 ARPDYNPPL 
                 5.7226 
                 2289 
                   
               
               
                   
                   
               
               
                   
                 22 
                 AYYSMVGNW 
                 5.7076 
                 360 
                 6.46991 
               
               
                   
                   
               
               
                   
                 23 
                 FLARLIWWL 
                 5.6847 
                 838 
                 6.17696 
               
               
                   
                   
               
               
                   
                 24 
                 SQLDLSGWF 
                 5.6728 
                 2962 
                   
               
               
                   
                   
               
               
                   
                 25 
                 SMLTDPSHI 
                 5.6657 
                 2173 
                 6.94013 
               
               
                   
                   
               
               
                   
                 26 
                 EYILLLFLL 
                 5.6643 
                 717 
                   
               
               
                   
                   
               
               
                   
                 27 
                 ILLGPADSF 
                 5.6526 
                 1010 
                 5.50208 
               
               
                   
                   
               
               
                   
                 28 
                 LNPSVAATL 
                 5.6281 
                 1254 
                   
               
               
                   
                   
               
               
                   
                 29 
                 GLLSFLVFF 
                 5.6226 
                 764 
                   
               
               
                   
                   
               
               
                   
                 30 
                 YVYDHLTPL 
                 5.6148 
                 948 
                   
               
               
                   
                   
               
               
                   
                 31 
                 HYAPRPCGI 
                 5.5954 
                 488 
                   
               
               
                   
                   
               
               
                   
                 32 
                 GLIHLHRNI 
                 5.595 
                 688 
                   
               
               
                   
                   
               
               
                   
                 33 
                 HYRDVLKEM 
                 5.5928 
                 2482 
                   
               
               
                   
                   
               
               
                   
                 34 
                 YYKVFLARL 
                 5.5825 
                 834 
                 7.24746 
               
               
                   
                   
               
               
                   
                 35 
                 CMVDYPYRL 
                 5.566 
                 607 
                   
               
               
                   
                   
               
               
                   
                 36 
                 AVIPDREVL 
                 5.5541 
                 1693 
                   
               
               
                   
                   
               
               
                   
                 37 
                 NFSRCWVAL 
                 5.5313 
                 234 
                 6.28275 
               
               
                   
                   
               
               
                   
                 38 
                 VFSDMETKL 
                 5.5307 
                 975 
                 7.30704 
               
               
                   
                   
               
               
                   
                 39 
                 VWPLLLLLL 
                 5.5297 
                 793 
                   
               
               
                   
                   
               
               
                   
                 40 
                 ITYSTYCKF 
                 5.5171 
                 1291 
                 6.97507 
               
               
                   
                   
               
               
                   
                 41 
                 IEPLDLPQI 
                 5.5049 
                 2873 
                   
               
               
                   
                   
               
               
                   
                 42 
                 LLSTTEWQI 
                 5.4989 
                 666 
                 8.33563 
               
               
                   
                   
               
               
                   
                 43 
                 PLLREEVVF 
                 5.4208 
                 2139 
                   
               
               
                   
                   
               
               
                   
                 44 
                 ATPPGSITV 
                 4.2466 
                 1349 
               
               
                   
                   
               
            
           
         
       
     
     The sequences of SEQ ID NOS: 1 to 44 are sequences consisting of 9 amino acid residues contained in a certain genome protein (SEQ ID NO: 184) of the HCV D90208 strain, which will be described later. The sequences of SEQ ID NOS: 1 to 44 are sequences predicted by the above-mentioned method to have superior binding to an HLA-A24 type molecule. SEQ ID NOS: 1 to 44 are arranged in decreasing binding order. That is, SEQ ID NO: 1 is the sequence that is predicted to have the best binding. A predicted score for binding to the HLA-A24 type molecule and binding experiment data for each sequence are expressed in the form of −log Kd values. 
     The sequences of SEQ ID NOS: 45 to 83 are given in Table 2 below. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 HLA-A24-BINDING PEPTIDE 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 SEQ 
                 D89815 
                 PRE- 
                   
                 BINDING 
               
               
                   
                 ID 
                 PREDICTED 
                 DICTED 
                 SEQ 
                 EXPERIMENT 
               
               
                   
                 NO 
                 SCORE 
                 SCORE 
                 NAME 
                 DATA 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 45 
                 VILDSFEPL 
                 6.4276 
                 2251 
                 5.00343 
               
               
                   
                   
               
               
                   
                 46 
                 ILPCSYTTL 
                 6.131 
                 674 
                   
               
               
                   
                   
               
               
                   
                 47 
                 FWAEHMWNF 
                 6.0822 
                 1760 
                   
               
               
                   
                   
               
               
                   
                 48 
                 ALYDVVSTL 
                 6.0484 
                 2593 
                 6.38942 
               
               
                   
                   
               
               
                   
                 49 
                 AFYGVWPLL 
                 5.9676 
                 789 
                 7.7344 
               
               
                   
                   
               
               
                   
                 50 
                 PYIEQGMQL 
                 5.9628 
                 1716 
                   
               
               
                   
                   
               
               
                   
                 51 
                 TPPAVPQTF 
                 5.9302 
                 1215 
                   
               
               
                   
                   
               
               
                   
                 52 
                 WHYPCTVNF 
                 5.921 
                 616 
                 6.38729 
               
               
                   
                   
               
               
                   
                 53 
                 GILPFFMFF 
                 5.9182 
                 764 
                 7.69551 
               
               
                   
                   
               
               
                   
                 54 
                 GLIHLHQNI 
                 5.879 
                 688 
                 5.85566 
               
               
                   
                   
               
               
                   
                 55 
                 LMCAVHPEL 
                 5.8442 
                 876 
                 6.59126 
               
               
                   
                   
               
               
                   
                 56 
                 TVLADFKTW 
                 5.8411 
                 1986 
                 6.51874 
               
               
                   
                   
               
               
                   
                 57 
                 AYSQQTRGL 
                 5.831 
                 1031 
                   
               
               
                   
                   
               
               
                   
                 58 
                 AQPGYPWPL 
                 5.8258 
                 77 
                 5.36419 
               
               
                   
                   
               
               
                   
                 59 
                 PLLRDEVTF 
                 5.8128 
                 2139 
                 5.08926 
               
               
                   
                   
               
               
                   
                 60 
                 ILMTHFFSI 
                 5.8071 
                 2843 
                 7.89519 
               
               
                   
                   
               
               
                   
                 61 
                 SYTWTGALI 
                 5.8059 
                 2422 
                 7.12954 
               
               
                   
                   
               
               
                   
                 62 
                 ATPPGSVTF 
                 5.7779 
                 1349 
                 6.51124 
               
               
                   
                   
               
               
                   
                 63 
                 LLPRRGPRL 
                 5.7503 
                 36 
                 7.71195 
               
               
                   
                   
               
               
                   
                 64 
                 LMTHFFSIL 
                 5.7443 
                 2844 
                 5.9169 
               
               
                   
                   
               
               
                   
                 65 
                 LLKRLHQWI 
                 5.7425 
                 1956 
                 6.85724 
               
               
                   
                   
               
               
                   
                 66 
                 ARPDYNPPL 
                 5.7226 
                 2289 
                   
               
               
                   
                   
               
               
                   
                 67 
                 AYYSMVGNW 
                 5.7076 
                 360 
                 6.46991 
               
               
                   
                   
               
               
                   
                 68 
                 KFPAAMPVW 
                 5.7062 
                 2280 
                   
               
               
                   
                   
               
               
                   
                 69 
                 QYTLLFNIL 
                 5.7028 
                 1804 
                   
               
               
                   
                   
               
               
                   
                 70 
                 LVPGAAYAF 
                 5.6865 
                 782 
                   
               
               
                   
                   
               
               
                   
                 71 
                 RYAPACKPL 
                 5.6851 
                 2132 
                 6.75756 
               
               
                   
                   
               
               
                   
                 72 
                 FLARLIWWL 
                 5.6847 
                 838 
                 6.17696 
               
               
                   
                   
               
               
                   
                 73 
                 SQLDLSGWF 
                 5.6728 
                 2962 
                   
               
               
                   
                   
               
               
                   
                 74 
                 SMLTDPSHI 
                 5.6657 
                 2173 
                 6.94014 
               
               
                   
                   
               
               
                   
                 75 
                 ILLGPADSF 
                 5.6526 
                 1010 
                 5.50208 
               
               
                   
                   
               
               
                   
                 76 
                 WLRDVWDWI 
                 5.6315 
                 1976 
                 6.34379 
               
               
                   
                   
               
               
                   
                 77 
                 YVVLLFLLL 
                 5.6308 
                 718 
                   
               
               
                   
                   
               
               
                   
                 78 
                 LNPSVAATL 
                 5.6281 
                 1254 
                   
               
               
                   
                   
               
               
                   
                 79 
                 YVYDHLTPL 
                 5.6148 
                 948 
                   
               
               
                   
                   
               
               
                   
                 80 
                 HYRDVLKEM 
                 5.5928 
                 2482 
                   
               
               
                   
                   
               
               
                   
                 81 
                 TLRRHVDLL 
                 5.5762 
                 257 
                   
               
               
                   
                   
               
               
                   
                 82 
                 AVIPDREVL 
                 5.5541 
                 1693 
                   
               
               
                   
                   
               
               
                   
                 83 
                 FLISQLFTF 
                 5.5528 
                 285 
               
               
                   
                   
               
            
           
         
       
     
     The sequences of SEQ ID NOS: 45 to 83 are sequences consisting of 9 amino acid residues contained in a certain genome protein (SEQ ID NO: 185) of the HCV D89815 strain. The sequences of SEQ ID NOS: 45 to 83 are sequences predicted by the above-mentioned method to have superior binding to an HLA-A24 type molecule. SEQ ID NOS: 45 to 83 are arranged in decreasing binding order. That is, SEQ ID NO: 45 is the sequence that is predicted to have the best binding. A predicted score for binding to the HLA-A24 type molecule and binding experiment data for each sequence are expressed in the form of −log Kd values. 
     The sequences of SEQ ID NOS: 84 to 123 are shown in Table 3 below. 
     
       
         
           
               
             
               
                 TABLE 3  
               
             
            
               
                   
               
               
                 HLA-A24-BINDING PEPTIDE 
               
            
           
           
               
               
               
               
               
            
               
                 SEQ 
                 pBRT703′ X 
                 PRE- 
                   
                 BINDING 
               
               
                 ID 
                 PREDICTED 
                 DICTED 
                 SEQ 
                 EXPERIMENT 
               
               
                 NO 
                 SCORE 
                 SCORE 
                 NAME 
                 DATA 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 84 
                 VILDSFEPL 
                 6.7012 
                 2251 
                 5.00343 
               
               
                   
               
               
                 85 
                 ILPCSYTTL 
                 6.2441 
                 674 
                   
               
               
                   
               
               
                 86 
                 GILPFFMFF 
                 6.1234 
                 764 
                 7.69551 
               
               
                   
               
               
                 87 
                 PLLRDEVTF 
                 6.0954 
                 2139 
                 5.08926 
               
               
                   
               
               
                 88 
                 TPPAVPQTF 
                 6.0934 
                 1215 
                   
               
               
                   
               
               
                 89 
                 FWAKHMWNF 
                 6.0822 
                 1760 
                   
               
               
                   
               
               
                 90 
                 TVLADFKTW 
                 5.9355 
                 1986 
                 6.51874 
               
               
                   
               
               
                 91 
                 ALYDVVSTL 
                 5.9179 
                 2593 
                 6.38942 
               
               
                   
               
               
                 92 
                 WHYPCTVNF 
                 5.8742 
                 616 
                 6.38729 
               
               
                   
               
               
                 93 
                 ATPPGSVTF 
                 5.8681 
                 1349 
                 6.51124 
               
               
                   
               
               
                 94 
                 GLIHLHQNI 
                 5.8476 
                 688 
                 5.85566 
               
               
                   
               
               
                 95 
                 AYSQQTRGL 
                 5.831 
                 1031 
                   
               
               
                   
               
               
                 96 
                 ILWTHFFSI 
                 5.8217 
                 2843 
                 7.89519 
               
               
                   
               
               
                 97 
                 FLARLIWWL 
                 5.7815 
                 838 
                 6.17698 
               
               
                   
               
               
                 98 
                 AFYGVWPLL 
                 5.7373 
                 789 
                 7.7344 
               
               
                   
               
               
                 99 
                 FLISQLFTF 
                 5.7341 
                 285 
                   
               
               
                   
               
               
                 100 
                 ILLGPADSF 
                 5.719 
                 1010 
                 5.50208 
               
               
                   
               
               
                 101 
                 SMLTDPSHI 
                 5.6922 
                 2173 
                 6.94014 
               
               
                   
               
               
                 102 
                 AYYSMVGNW 
                 5.6746 
                 360 
                 6.46991 
               
               
                   
               
               
                 103 
                 QYTLLFNIL 
                 5.6682 
                 1804 
                   
               
               
                   
               
               
                 104 
                 LLKRLHQWI 
                 5.6343 
                 1956 
                 6.85724 
               
               
                   
               
               
                 105 
                 SQLDLSGWF 
                 5.5993 
                 2962 
                   
               
               
                   
               
               
                 106 
                 WLRDVWDWI 
                 5.5818 
                 1976 
                 6.34379 
               
               
                   
               
               
                 107 
                 ITYSTYGKF 
                 5.5352 
                 1291 
                 6.37373 
               
               
                   
               
               
                 108 
                 SYTWTGALI 
                 5.5253 
                 2422 
                 7.12954 
               
               
                   
               
               
                 109 
                 LLSTTEWQI 
                 5.5182 
                 666 
                 8.33563 
               
               
                   
               
               
                 110 
                 RAPACKPL 
                 5.5076 
                 2132 
                 6.75756 
               
               
                   
               
               
                 111 
                 RLIWWLQYF 
                 5.5035 
                 841 
                   
               
               
                   
               
               
                 112 
                 VLADFKTWL 
                 5.4871 
                 1987 
                 6.63423 
               
               
                   
               
               
                 113 
                 LVPGAAYAF 
                 5.4661 
                 782 
                   
               
               
                   
               
               
                 114 
                 DLPQIIQRL 
                 5.4605 
                 2877 
                   
               
               
                   
               
               
                 115 
                 WICTVLADF 
                 5.4521 
                 1983 
                   
               
               
                   
               
               
                 116 
                 FYGVWPLLL 
                 5.4409 
                 790 
                   
               
               
                   
               
               
                 117 
                 LLLSILGPL 
                 5.4365 
                 891 
                   
               
               
                   
               
               
                 118 
                 HYRDVLKEM 
                 5.4331 
                 2482 
                   
               
               
                   
               
               
                 119 
                 LIWWLQYFI 
                 5.4328 
                 842 
                   
               
               
                   
               
               
                 120 
                 AVIPDREVL 
                 5.4247 
                 1693 
                   
               
               
                   
               
               
                 121 
                 TRPPHGNWF 
                 5.4243 
                 542 
                   
               
               
                   
               
               
                 122 
                 KFPAAMPVW 
                 5.424 
                 2280 
                   
               
               
                   
               
               
                 123 
                 VFPDLGVRV 
                 5.3898 
                 2580 
                 6.73918 
               
               
                   
               
            
           
         
       
     
     The sequences of SEQ ID NOS: 84 to 123 are sequences consisting of 9 amino acid residues contained in a certain genome protein (SEQ ID NO: 186) of the HCV pBRT703′X strain, which will be described later. The sequences of SEQ ID NOS: 84 to 123 are sequences predicted by the above-mentioned method to have superior binding to an HLA-A24 type molecule. SEQ ID NOS: 84 to 123 are arranged in decreasing binding order. That is, SEQ ID NO: 84 is the sequence that is predicted to have the best binding. A predicted score for the binding to the HLA-A24 type molecule and binding experiment data for each sequence are expressed in the form of −log Kd values. 
     The sequences of SEQ ID NOS: 124 to 183 are shown in Table 4 below. 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 HLA-A2-BINDING PEPTIDE 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 SEQ 
                 pBRT703′ X 
                 PRE- 
                   
                 BINDING 
               
               
                   
                 ID 
                 PREDICTED 
                 DICTED 
                 SEQ 
                 EXPERIMENT 
               
               
                   
                 NO 
                 SCORE 
                 SCORE 
                 NAME 
                 DATA 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 124 
                 KLLPRLPGV 
                 5.9316 
                 1998 
                 6.70726 
               
               
                   
                 125 
                 DMPSTEDLV 
                 5.925 
                 1872 
                   
               
               
                   
                 126 
                 YLYGIGSAV 
                 5.8812 
                 701 
                 5.56617 
               
               
                   
                 127 
                 YLNTPGLPV 
                 5.7437 
                 1542 
                 5.67247 
               
               
                   
                 128 
                 CLLLLSVGV 
                 5.7302 
                 2994 
                   
               
               
                   
                 129 
                 LLLSVGVGI 
                 5.6529 
                 2996 
                   
               
               
                   
                 130 
                 LLCPSGHVV 
                 5.6239 
                 1169 
                   
               
               
                   
                 131 
                 AILSPGALV 
                 5.6128 
                 1885 
                 6.24349 
               
               
                   
                 132 
                 SLIRVPYFV 
                 5.5906 
                 905 
                 5.86299 
               
               
                   
                 133 
                 DVWDWICTV 
                 5.5657 
                 1979 
                 4.97956 
               
               
                   
                 134 
                 VIPASGDVV 
                 5.558 
                 1425 
                 6.24145 
               
               
                   
                 135 
                 RALAHGVRV 
                 5.5481 
                 149 
                 5.28381 
               
               
                   
                 136 
                 LSDGSWSTV 
                 5.5257 
                 2400 
                 6.22313 
               
               
                   
                 137 
                 KLQDCTMLV 
                 5.4922 
                 2726 
                 5.25202 
               
               
                   
                 138 
                 YCLTTGSVV 
                 5.4899 
                 1673 
                   
               
               
                   
                 139 
                 SMLTDPSHI 
                 5.4685 
                 2173 
                 5.55941 
               
               
                   
                 140 
                 AAFCSAMYV 
                 5.4454 
                 269 
                   
               
               
                   
                 141 
                 YSPGEINRV 
                 5.4058 
                 2896 
                 6.05123 
               
               
                   
                 142 
                 YTNVDQDLV 
                 5.4046 
                 1101 
                 5.67802 
               
               
                   
                 143 
                 LRDEVTFQV 
                 5.4015 
                 2141 
                   
               
               
                   
                 144 
                 LAALTGTYV 
                 5.3812 
                 941 
                   
               
               
                   
                 145 
                 CEPEPDVTV 
                 5.3645 
                 2162 
                   
               
               
                   
                 146 
                 CMSADLEVV 
                 5.3561 
                 1648 
                 4.80983 
               
               
                   
                 147 
                 VFPDLGVRV 
                 5.3546 
                 2580 
                 6.02403 
               
               
                   
                 148 
                 YCFTPSPVV 
                 5.3206 
                 507 
                   
               
               
                   
                 149 
                 VLQASLIRV 
                 5.2832 
                 901 
                 5.46327 
               
               
                   
                 150 
                 KQAEAAAPV 
                 5.2619 
                 1741 
                 5.41584 
               
               
                   
                 151 
                 LLLALPPRA 
                 5.2556 
                 799 
                   
               
               
                   
                 152 
                 VLDDHYRDV 
                 5.2542 
                 2478 
                 6.51154 
               
               
                   
                 153 
                 FSPRRHETV 
                 5.2377 
                 293 
                   
               
               
                   
                 154 
                 SVIDCNTCV 
                 5.2251 
                 1450 
                   
               
               
                   
                 155 
                 GLIRACTLV 
                 5.1743 
                 917 
                   
               
               
                   
                 156 
                 TVNFTIFKV 
                 5.1707 
                 621 
                   
               
               
                   
                 157 
                 EMGGNITRV 
                 5.1651 
                 2236 
                   
               
               
                   
                 158 
                 TVNFTIFKV 
                 5.1643 
                 2448 
                   
               
               
                   
                 159 
                 QLDLSGWFV 
                 5.1635 
                 2963 
                   
               
               
                   
                 160 
                 TLAARNASV 
                 5.1583 
                 245 
                   
               
               
                   
                 161 
                 RLGAVQNEV 
                 5.1396 
                 1627 
                   
               
               
                   
                 162 
                 VILDSFEPL 
                 5.138 
                 2251 
                 5.38729 
               
               
                   
                 163 
                 AALENLVVL 
                 5.1347 
                 746 
                   
               
               
                   
                 164 
                 LLEDTDTPI 
                 5.1223 
                 2545 
                   
               
               
                   
                 165 
                 VVTSTWVLV 
                 5.1189 
                 1655 
                   
               
               
                   
                 166 
                 FSLDPTFTI 
                 5.1183 
                 1464 
                   
               
               
                   
                 167 
                 TIPASAYEV 
                 5.1158 
                 186 
                   
               
               
                   
                 168 
                 DLLEDTDTP 
                 5.091 
                 2544 
                   
               
               
                   
                 169 
                 LLLSILGPL 
                 5.0753 
                 891 
                   
               
               
                   
                 170 
                 VLADFKTWL 
                 5.0725 
                 1987 
                 6.01696 
               
               
                   
                 171 
                 SILGIGTVL 
                 5.071 
                 1325 
                   
               
               
                   
                 172 
                 AGDNFPYLV 
                 5.0651 
                 1579 
                   
               
               
                   
                 173 
                 ILPCSYTTL 
                 5.0643 
                 674 
                 6.37008 
               
               
                   
                 174 
                 VAAEEYVEV 
                 5.0509 
                 2085 
                   
               
               
                   
                 175 
                 LAVAVEPVV 
                 5.0484 
                 967 
                   
               
               
                   
                 176 
                 ALYDVVSTL 
                 5.0301 
                 2593 
                 6.14967 
               
               
                   
                 177 
                 FLARLIWWL 
                 5.0259 
                 838 
                 5.67557 
               
               
                   
                 178 
                 RLLAPITAY 
                 5.0244 
                 1024 
                   
               
               
                   
                 179 
                 WLRDVWDWI 
                 5.0191 
                 1976 
                 5.68156 
               
               
                   
                 180 
                 CVNGACWTV 
                 5.0181 
                 1073 
                   
               
               
                   
                 181 
                 YVYDHLTPL 
                 5.0087 
                 948 
                   
               
               
                   
                 182 
                 TVVLTESTV 
                 5.0061 
                 2332 
                   
               
               
                   
                 183 
                 AARALAHGV 
                 5.0044 
                 147 
               
               
                   
                   
               
            
           
         
       
     
     The sequences of SEQ ID NOS: 124 to 183 are sequences consisting of 9 amino acid residues contained in a certain genome protein (SEQ ID NO: 186) of the HCV pBRT703′X strain, which will be described later. The sequences of SEQ ID NOS: 124 to 183 are sequences predicted by the above-mentioned method to have superior binding to an HLA-A2 type molecule. SEQ ID NOS: 124 to 183 are arranged in decreasing binding order. That is, SEQ ID NO: 124 is the sequence that is predicted to have the best binding. A predicted score for the binding to the HLA-A2 type molecule and binding experiment data for each sequence are expressed in the form of −log Kd values. 
     Although details are described later, it is clear that in all of Table 1 to Table 4, there is a correlation between the predicted score and the binding experiment data. That is, although there are slight errors, it can be said that a peptide that is predicted by the above-mentioned method to have high binding to the HLA-A type molecule is found experimentally to have high binding to the HLA-A type molecule. 
     Since there is no conventional technique for discovering an HLA-binding peptide by utilizing such an experimental design method, there are only a very small number of HLA-binding peptides that have been experimentally confirmed to have HLA-binding properties. Because of this, even when a peptide consisting of 9 amino acid residues is randomly synthesized by a conventional method, and subjected to an experiment to find out if it binds to an HLA molecule, there is a probability of only about 1 in 100 of finding one that has a binding in terms of a −log Kd value, exceeding 6. 
     In accordance with this embodiment, since the technique of finding an HLA-binding peptide by utilizing the experimental design method is used, as described above, as many as 183 sequences of HLA-binding peptides can be found. Furthermore, when the binding of some of the HLA-binding peptides obtained is experimentally examined, it is confirmed that all of the sequences that have been subjected to the experiment exhibit an excellent binding to HLA that is equal to or higher than that predicted. 
     Among these sequences, an HLA-binding peptide containing at least one type of amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 2, 3, 5, 8, 12, 13, 14, 16, 17, 18, 19, 22, 23, 25, 27, 34, 37, 38, 40, 42, 45, 48, 49, 52, 53, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 65, 67, 71, 72, 74, 75, 76, 84, 86, 87, 90, 91, 92, 93, 94, 96, 97, 98, 100, 101, 102, 104, 106, 107, 108, 109, 110, 112, 123, 124, 126, 127, 131, 132, 133, 134, 135, 136, 137, 139, 141, 142, 146, 147, 149, 150, 152, 162, 170, 173, 176, 177, and 179 is experimentally confirmed to bind to a human HLA-A type molecule. It can therefore be said with certainty that it is an HLA-binding peptide that has excellent properties in binding to a human HLA-A type molecule. 
     The binding to an HLA molecule of the HLA-binding peptide related to the present embodiment is 3 or greater in term of a −log Kd value, particularly preferably 5 or greater, and more preferably 5.4 or greater. 
     In the field of biochemistry, it is known that a binding ability in terms of a −log Kd value, of about 3 is the threshold level for whether or not a peptide actually binds to an MHC such as an HLA. Therefore, if the binding to an HLA molecule in terms of a −log Kd value, is 3 or greater, it can be said that it is an HLA-binding peptide. 
     Furthermore, if the binding to an HLA molecule in terms of a −log Kd value, is 5 or greater, since the peptide obtained has excellent properties in binding to the HLA molecule, it can suitably be used for development of an effective therapeutic drug, prophylactic drug and the like for an immune disease and the like. 
     Moreover, if the binding to an HLA molecule in terms of a −log Kd value, is 5.4 or greater, the peptide obtained has particularly good properties in binding to the HLA molecule, and it can suitably be used for the development of an even more effective therapeutic drug, preventive drug and the like for an immune disease and the like. 
     Furthermore, it may be arranged that the HLA-binding peptide related to the present embodiment consists of not less than 8 and not more than 11 amino acid residues. 
     In this way, if the peptide consists of not less than 8 and not more than 11 amino acid residues, it has excellent properties in binding to an HLA molecule. Furthermore, the cytotoxic T lymphocyte (CTL) specifically recognizes a virus antigen (CTL epitope) consisting of 8 to 11 amino acids presented in an HLA class I molecule on the surface of a cell infected with a virus and the like, and eliminates the virus by damaging the infected cell. It is important to prepare such a CTL epitope consisting of 8 to 11 amino acids that is specific to a virus and the like in order to prepare a vaccine for therapy or prevention against the virus and the like. 
     For example, the above-mentioned HLA-binding peptide may be a peptide consisting of amino acid residues alone, but it is not particularly limited thereto. For example, it may be an HLA-binding peptide precursor that is optionally modified with a sugar chain or a fatty acid group or the like as long as the effects of the present invention are not impaired. Such a precursor is subjected to a change involving digestion by a digestive enzyme and the like in a living mammalian body such as in a human digestive organ to become an HLA-binding peptide, thus exhibiting the similar effects to those shown by the above-mentioned HLA-binding peptide. 
     Furthermore, the above-mentioned HLA-binding peptide may be a peptide that binds to a human HLA-A24 type molecule. 
     Moreover, the above-mentioned HLA-binding peptide may be a peptide that binds to a human HLA-A2 type molecule. 
     In accordance with this constitution, since a peptide is obtained that binds to an HLA-A24 type molecule, which is often seen in Asian people, such as Japanese people, it can be utilized in the development of a therapeutic drug, a preventive drug and the like that is particularly effective for Asian people, such as Japanese people. 
     Furthermore, in accordance with this constitution, since a peptide is obtained that binds to an HLA-A2 type molecule, which is often seen in European and American people in addition to Japanese people, it can be utilized in the development of a therapeutic drug, a preventive drug and the like that is particularly effective for European and American people in addition to Japanese people. 
     The amino acid sequence contained in the above-mentioned HLA-binding peptide may be an amino acid sequence derived from a certain genome protein of HCV, but it is not particularly limited thereto. For example, it may be an amino acid sequence derived from an HIV protein, an amino acid sequence derived from a cedar pollen protein and the like. Moreover, it may contain an amino acid sequence derived from a protein having the other pathogenicity or allergenicity. 
     For example, when it contains an amino acid sequence derived from an HCV envelope protein, an HLA-binding peptide that can be utilized in the prevention, therapy and the like of a disease caused by HCV can be obtained. 
     Embodiment 2 
     In accordance with this embodiment, there is provided an HLA-binding peptide that binds to an HLA-A type molecule, contains an amino acid sequence formed by deletion, substitution, or addition of one or two amino acid residues of the amino acid sequence contained in the above-mentioned HLA-binding peptide, and consists of not less than 8 and not more than 11 amino acid residues. 
     As described later, even though the constitution includes an amino acid sequence formed by deletion, substitution, or addition of one or a few amino acid residues of a specific amino acid sequence that binds to an HLA-A type molecule, the similar effects to those of the HLA-binding peptide related to the above-mentioned embodiment 1 are exhibited. 
     Although the amino acid sequences of polyproteins of the above-mentioned HCV D90208 strain, D89815 strain, and pBRT703′X strain (mutant subclone of D89815) are different from each other in part, since the correlation between predicted data and experimental data for the −log Kd value of several 9-mer peptides existing in a certain genome protein of the D90208 strain is high, that is, a sequence that is determined to be binding based on predicted data shows a good −log Kd value in experimental data, it can be predicted that the D89815 strain and the pBRT703′X strain (mutant subclone of D89815) will show a −log Kd value with a superior ranking in the predicted data. Therefore, it can be predicted that even amino acid sequences in a certain genome proteins of the D89815 strain and the pBRT703′X strain (mutant subclone of D89815), which are amino acid sequences formed by substitution of one or two amino acid residues of the amino acid sequences that exhibit binding properties, will similarly show excellent HLA-binding properties. 
     That is, it can be predicted that even an amino acid sequence formed by deletion, substitution, or addition of one or two amino acid residues of an amino acid sequence shown in SEQ ID NOS: 1 to 183 that has excellent properties in binding to an HLA-A type molecule will show excellent HLA-binding properties in the similar manner. 
     From another viewpoint, it can be predicted that even an amino acid sequence formed by deletion, substitution, or addition of one or a few amino acid residues of an amino acid sequence predicted by the above-mentioned method to have excellent properties in binding to an HLA-A type molecule will show excellent HLA-binding properties in the similar manner. The amino acid residues that are substituted are preferably amino acid residues having similar properties to each other, such that both are hydrophobic amino acid residues. 
     Moreover, the HLA-binding peptides described in Embodiment 1 and Embodiment 2 can be produced using a method known to a person skilled in the art. For example, they may be artificially synthesized by a solid-phase method or a liquid-phase method. Alternatively, these HLA-binding peptides may be produced by expressing them from a DNA segment or a recombinant vector coding for these HLA-binding peptides. These HLA-binding peptides thus obtained can be identified by a method known to a person skilled in the art. For example, identification is possible by use of Edman degradation, mass spectrometry and the like. 
     Embodiment 3 
     In accordance with the present embodiment, there is provided a DNA segment containing a DNA sequence coding for the above-mentioned HLA-binding peptide. Since the DNA segment related to the present embodiment contains a specific DNA sequence, it can express the above-mentioned HLA-binding peptide. 
     When the above-mentioned HLA-binding peptide is expressed by using the DNA segment related to the present embodiment, expression may be carried out by incorporating this DNA segment into a cell, or expression may be carried out by using a commercial artificial protein expression kit. 
     Furthermore, continuous expression may be carried out by incorporating the above-mentioned DNA segment into, for example, a human cell. Because of this, an HLA-binding peptide can be made to be present constitutively within a cell by incorporating a DNA segment coding for the HLA-binding peptide into the cell rather than incorporating the HLA-binding peptide itself into the cell. When an HLA-binding peptide is used as a vaccine, such an ability to express constitutively is advantageous in terms of enhancing the efficacy of the vaccine. 
     Moreover, the DNA segment related to the present embodiment can be produced by a method known to a person skilled in the art. For example, it may be artificially synthesized by means of a commercial DNA synthesizer and the like. Alternatively, it may be segmented from the HCV genome by using a restriction enzyme and the like. Alternatively, it may be amplified from the HCV genome by a PCR method using a pair of primers. The DNA segment thus obtained may be identified using a method known to a person skilled in the art. For example, it may be identified by a commercial DNA sequencer. 
     Embodiment 4 
     In accordance with the present embodiment, there is provided a recombinant vector that contains a DNA sequence coding for the above-mentioned HLA-binding peptide. Since the recombinant vector related to the present embodiment contains a specific DNA sequence, the above-mentioned HLA-binding peptide can be expressed. 
     When the above-mentioned HLA-binding peptide is expressed by using the recombinant vector related to the present embodiment, expression may be carried out by incorporating this recombinant vector into a cell, or expression may be carried out by using a commercial artificial protein expression kit. 
     Furthermore, continuous expression may be carried out by incorporating the above-mentioned recombinant vector into, for example, a human cell. Because of this, the HLA-binding peptide can be made to be present continuously within a cell by incorporating a recombinant vector coding for the HLA-binding peptide into the cell rather than incorporating the HLA-binding peptide itself into the cell. When the HLA-binding peptide is used as a vaccine, such an ability to express continuously is advantageous in terms of enhancing the efficacy of the vaccine. 
     Furthermore, in the above-mentioned recombinant vector, the amount of HLA-binding peptide expressed can be controlled with high precision by the use of a certain sequence in a regulatory region involved in transcription and expression, such as a promoter region upstream of a DNA sequence coding for the above-mentioned HLA-binding peptide. Moreover, the number of copies of a recombinant vector in a cell can be controlled with high precision by the use of a certain sequence in a regulatory region involved in replication, such as the origin region of the recombinant vector. 
     Furthermore, the above-mentioned recombinant vector may freely contain a sequence other than the DNA sequence coding for the above-mentioned HLA-binding peptide. For example, it may contain a sequence of a marker gene such as a drug resistance gene. 
     Moreover, the recombinant vector related to the present embodiment can be produced using a method known to a person skilled in the art. For example, it may be obtained by cleaving a multicloning site of a commercial vector such as pBR322 or pUC19 at a certain restriction enzyme site, and inserting the above-mentioned DNA segment into the site and carrying out ligation. Furthermore, the recombinant vector thus obtained can be identified using a method known to a person skilled in the art. For example, it can be confirmed by agarose gel electrophoresis whether or not the length of the DNA segment cleaved by a predetermined restriction enzyme coincides with the restriction map of a commercial vector such as pBR322 or pUC19 and, furthermore, it can be identified by a DNA sequencer and the like whether or not the above-mentioned DNA sequence is contained in the DNA sequence cut out from the multicloning site. 
     Although embodiments of the present invention are described above, they are illustrated as examples of the present invention, and various constitutions other than the above may be employed. 
     For example, in the above-mentioned embodiments, the HLA-binding peptide contains an amino acid sequence derived from a certain genome protein (SEQ ID NOS: 184, 185, 186) of HCV, but an HLA-binding peptide containing an amino acid sequence derived from another HCV protein may be used. In such a case, it can be used for the therapy of various types of immune diseases related to the protein from which it is derived. 
     Furthermore, an HLA-binding peptide for a pathogen other than HCV, such as an HIV virus, may be employed, and an HLA-binding peptide containing an amino acid sequence derived from a protein such as a cedar pollen allergen and the like, or a cancer cell may be employed. 
     In this way, if an amino sequence that is predicted by the above-mentioned method to have excellent HLA-binding properties is contained, it can be expected that it will exhibit excellent HLA-binding properties in the similar way when confirmation is carried out experimentally. Because of this, these HLA-binding peptides can suitably be used mainly for the therapy or prevention of infectious diseases (influenza, SARS, HIV, HCV and the like), and also for cancer immunotherapy, allergic diseases (pollen allergy (hay fever), rheumatism, atopy, asthma and the like), autoimmune diseases and the like. 
     EXAMPLES 
     The present invention is further explained below by reference to Examples, but the present invention is not limited thereto. 
     Specifically, procedures of prediction, experiment, and evaluation in the present examples were carried out based on an active learning experiment design, and in general the following steps were repeated. A schematic drawing for the active learning experiment design employed here is shown in  FIG. 1 . 
     (1) A trial of a lower-order learning algorithm, which will be described later, was carried out once. That is, a plurality of hypotheses were generate by random sampling from accumulated data and, with regard to randomly expressed candidate query points (peptide), a point that showed the largest distribution of predicted values was selected as a query point to be subjected to an experiment.
 
(2) The peptide at the selected query point was prepared by a synthesis and purification method, which will be described later, and the actual binding ability was measured by an experiment, which will be described later, and added to accumulated data.
 
     In the present example, as the lower-order learning algorithm, a supervised learning algorithm of a Hidden Markov Model was used, and 20 to 30 types of peptides were predicted and selected per experiment by starting with the initial data for 223 types of peptides; the above-mentioned procedure was repeated four times, and a total of 341 data points were obtained. 
     More specifically, in the active learning method of the present example, 20 to 30 types of peptides containing an amino acid sequence in which 9 of 20 types of amino acids were arranged were designed and synthesized per experiment. The strength of binding (binding ability) thereof to an HLA molecule was measured. The binding ability (Kd value in molar concentration) was obtained as an experimental result. When the binding ability was high, the peptide was selected as a candidate for an HLA-binding peptide that could be used as a material for a vaccine. 
     The results thus obtained were inputted into a learning system equipped with a learning machine employing the Hidden Markov Model as a mathematical algorithm, and rules were created. The learning machine sampled different results to prepare the rules. The rules expressed by the learning machine had different constitutions. The rules thus obtained and experimental data were stored as needed as accumulated data. 
     From among more than 20 9 =500 billion peptide sequences, candidates for a subsequent experiment were selected by the rules, and the above-mentioned process was repeated. In this stage, different rules were applied to experimental candidates, and the candidates for which predictions of the experimental results were divided were subjected to experiment. In this way, since the candidates for which predictions of the experimental results were divided were subjected to subsequent experiment, the final precision of the prediction was increased. 
     In this way, a plurality of learning machines carried out selective sampling in which samples that would give different predictions were selected as experimental candidates, information could be gained efficiently, and a hypothesis (rule) with high precision could be obtained. Repeating the above-mentioned process four times gave excellent results as in Examples described later. Repeating it seven times or more gave even better results. 
     In accordance with such an active learning method, the number of repetitions of the binding experiment for peptides consisting of 9 amino acid residues, which would otherwise have to be carried out for the 500 billion or more combinations of all the candidates for HLA-binding peptides, could be reduced. In the active learning method, a rule was formed by experiment, and the experiment was repeated for tens of sequence candidates that were predicted by applying the rule. Because of this, the number of experiments could be cut, and the time and cost of the initial screening could be greatly reduced. 
     Furthermore, the hit rate for prediction of the binding of a peptide to HLA by the rule obtained by the active learning method reached 70 to 80%, whereas the hit rate by other known techniques such as the anchor method was as low as about 30%. 
     &lt;Synthesis and Purification of Peptide&gt; 
     A peptide was manually synthesized by the Merrifield solid-phase method using Fmoc amino acids. After deprotection, reverse phase HPLC purification was carried out using a C18 column to give a purity of 95% or higher. Identification of the peptide and confirmation of its purity were carried out using a MALDI-TOF mass spectrometer (Voyager DE RP, PerSeptive). Quantitative analysis of the peptide was carried out by a Micro BCA assay (Pierce Corp.) using BSA as a standard protein. 
     &lt;Experiment of Binding Peptide to HLA-A24 Type Molecule&gt; 
     The ability of a peptide to bind to an HLA-A24 type molecule, which is a product of the HLA-A*2402 gene, was measured using C1R-A24 cells expressing the HLA-A24 type molecule (cells prepared by Professor Masafumi Takiguchi, Kumamoto University being supplied with permission by Assistant Professor Masaki Yasukawa, Ehime University). 
     C1R-A24 cells were first exposed to acidic conditions at a pH of 3.3 for 30 seconds, thus dissociating and removing a light chain β2m, which is associated with HLA class I molecules in common, and an endogenous peptide originally bound to the HLA-A*2402 molecule. After neutralization, purified β2m was added to C1R-A24 cells, and the obtained product was added to serial dilutions of a peptide, and incubated on ice for 4 hours. Staining was carried out using fluorescently labeled monoclonal antibody 17A12, which recognizes association (MHC-pep) of the three members, that is, HLA-A*2402 molecule, the peptide, and β2m, which had reassociated during the incubation. 
     Subsequently, the MHC-pep count per C1R-A24 cell (proportional to the strength of fluorescence of the above-mentioned fluorescent antibody) was quantitatively measured using an FACScan fluorescence-activated cell sorter (Becton Dickinson Biosciences). A binding dissociation constant Kd value between the HLA-A24 type molecule and the peptide was calculated from the average strength of fluorescence per cell by a published method (Udaka et al., Immunogenetics, 51, 816-828, 2000). 
     &lt;Experiment of Binding Peptide to HLA-A2 Type Molecule&gt; 
     The ability of a peptide to bind to an HLA-A2 type molecule, which is a product of the HLA-A*0201 gene, was measured using strain JY cells expressing the HLA-A*0201. 
     JY cells were first exposed to acidic conditions at a pH of 3.8 for 30 seconds, thus dissociating and removing a light chain β2m and an endogenous peptide, which were noncovalently associated with the HLA-A*0201 molecule. After neutralization, a reassociation experiment was carried out. 
     The above-mentioned JY cells and the purified β2m were added to stepped serial dilutions of peptide for which the binding ability would be measured, and incubation was carried out on ice for 4 hours. HLA-A*0201 molecules that had reassociated up to this point were stained using the associating type specific fluorescently-labeled monoclonal antibody BB7.2. 
     Subsequently, the amount of fluorescence per a cell was measured using a flow cytometer and a dissociation constant Kd value in molar concentration was calculated by a published method (Udaka et al., Immunogenetics, 51, 816-828, 2000). 
     &lt;Evaluation Results&gt; 
     The prediction results and the experimental results shown in Tables 1 to 4 above were obtained. 
     The sequences of SEQ ID NOS: 1 to 44 in Table 1 are sequences consisting of 9 amino acid residues contained in the full-length sequence of a certain genome protein of the HCV D90208 strain registered in the GenBank. Furthermore, the sequences of SEQ ID NOS: 1 to 44 are sequences having superior binding to an HLA-A24 type molecule as predicted by a hypothesis obtained by the experimental design method explained in Embodiment 1. SEQ ID NOS: 1 to 44 are arranged in decreasing binding order. That is, SEQ ID NO: 1 is the sequence that is predicted to have the best binding. The full-length amino acid sequence of the certain genome protein of the HCV D90208 strain is shown in SEQ ID NO: 184 
     
       
         
           
               
               
            
               
                 (MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERS 
                   
               
               
                   
               
               
                 QPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGMGWAGWLLSPRGSRPSWGPTDPR 
               
               
                   
               
               
                 RRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLP 
               
               
                   
               
               
                 GCSFSIFLLALLSCLTIPASAYEVRNVSGIYHVTNDCSNSSIVYEAADMIMHTPGCV 
               
               
                   
               
               
                 PCVRESNFSRCWVALTPTLAARNSSIPTTTIRRHVDLLVGAAALCSAMYVGDLCGSV 
               
               
                   
               
               
                 FLVSQLFTFSPRRYETVQDCNCSIYPGHVSGHRMAWDMMMNWSPTTALVVSQLLRIP 
               
               
                   
               
               
                 QAVVDMVAGAHWGVLAGLAYYSMVGNWAKVLIVMLLFAGVDGHTHVTGGRVASSTQS 
               
               
                   
               
               
                 LVSWLSQGPSQKIQLVNTNGSWHINRTALNCNDSLQTGFIAALFYAHRFNASGCPER 
               
               
                   
               
               
                 MASCRPIDEFAQGWGPITHDMPESSDQRPYCWHYAPRPCGIVPASQVCGPVYCFTPS 
               
               
                   
               
               
                 PVVVGTTDRFGAPTYSWGENETDVLLLSNTRPPQGNWFGCTWMNSTGFTKTCGGPPC 
               
               
                   
               
               
                 NIGGVGNNTLVCPTDCFRKHPEATYTKCGSGPWLTPRCMVDYPYRLWHYPCTVNFTV 
               
               
                   
               
               
                 FKVRMYVGGVEHRLNAACNWTRGERCDLEDRDRSELSPLLLSTTEWQILPCSFTTLP 
               
               
                   
               
               
                 ALSTGLIHLHRNIVDVQYLYGIGSAVVSFAIKWEYILLLFLLLADARVCACLWMMLL 
               
               
                   
               
               
                 IAQAEATLENLVVLNAASVAGAHGLLSFLVFFCAAWYIKGRLVPGAAYALYGVWPLL 
               
               
                   
               
               
                 LLLLALPPRAYAMDREMAASCGGAVFVGLVLLTLSPYYKVFLARLIWWLQYFITRAE 
               
               
                   
               
               
                 AHLQVWVPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLMVLQAGITRVPY 
               
               
                   
               
               
                 FVRAQGLIRACMLVRKVAGGHYVQMAFMKLAALTGTYVYDHLTPLRDWAHAGLRDLA 
               
               
                   
               
               
                 VAVEPVVFSDMETKLITWGADTAACGDIISGLPVSARRGKEILLGPADSFGEQGWRL 
               
               
                   
               
               
                 LAPITAYSQQTRGLLGCIITSLTGRDKNQVDGEVQVLSTATQSFLATCVNGVCWTVY 
               
               
                   
               
               
                 HGAGSKTLAGPKGPITQMYTNVDQDLVGWPAPPGARSMTPCTCGSSDLYLVTRHADV 
               
               
                   
               
               
                 VPVRRRGDSRGSLLSPRPISYLKGSSGGPLLCPSGHVVGIFRAAVCTRGVAKAVDFI 
               
               
                   
               
               
                 PVESMETTMRSPVFTDNSSPPAVPQTFQVAHLHAPTGSGKSTKVPAAYAAQGYKVLV 
               
               
                   
               
               
                 LNPSVAATLGFGAYMSKAHGIEPNIRTGVRTITTGGPITYSTYCKFLADGGCSGGAY 
               
               
                   
               
               
                 DIIICDECHSTDSTTILGIGTVLDQAETAGARLVVLATATPPGSITVPHPNIEEVAL 
               
               
                   
               
               
                 SNTGEIPFYGKAIPIEAIKGGRHLIFCHSKKKCDELAAKLTGLGLNAVAYYRGLDVS 
               
               
                   
               
               
                 VIPTSGDVVVVATDALMTGFTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDA 
               
               
                   
               
               
                 VSRAQRRGRTGRGRSGIYRFVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVR 
               
               
                   
               
               
                 LRAYLNTPGLPVCQDHLEFWESVFTGLTHIDAHFLSQTKQAGDNLPYLVAYQATVCA 
               
               
                   
               
               
                 RAQAPPPSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMACMSAD 
               
               
                   
               
               
                 LEVVTSTWVLVGGVLAALAAYCLTTGSVVIVGRIILSGRPAVIPDREVLYQEFDEME 
               
               
                   
               
               
                 ECASHLPYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPVVESKWRALEVFWAKHMW 
               
               
                   
               
               
                 NFISGIQYLAGLSTLPGNPAIASLMAFTASITSPLTTQNTLLFNILGGWVAAQLAPP 
               
               
                   
               
               
                 SAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKVMSGEMPSTEDLV 
               
               
                   
               
               
                 NLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPE 
               
               
                   
               
               
                 SDAAARVTQILSSLTITQLLKRLHQWINEDCSTPCSGSWLKDVWDWICTVLSDFKTW 
               
               
                   
               
               
                 LQSKLLPRLPGLPFLSCQRGYKGVWRGDGIMQTTCPCGAQITGHVKNGSMRIVGPKT 
               
               
                   
               
               
                 CSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAEEYVEVTRVGDFHYVTGMTTD 
               
               
                   
               
               
                 NVKCPCQVPAPEFFTEVDGVRLHRYAPVCKPLLREEVVFQVGLNQYLVGSQLPCEPE 
               
               
                   
               
               
                 PDVAVLTSMLTDPSHITAETAKRRLARGSPPSLASSSASQLSAPSLKATCTTHHDSP 
               
               
                   
               
               
                 DADLIEANLLWRQEMGGNITRVESENKVVILDSFDPIRAVEDEREISVPAEILRKPR 
               
               
                   
               
               
                 KFPPALPIWARPDYNPPLLESWKDPDYVPPVVHGCPLPSTKAPPIPPPRRKRTVVLT 
               
               
                   
               
               
                 ESTVSSALAELATKTFGSSGSSAVDSGTATGPPDQASDDGDKGSDVESYSSMPPLEG 
               
               
                   
               
               
                 EPGDPDLSDGSWSTVSGEAGEDVVCCSMSYTWTGALITPCAAEESKLPINPLSNSLL 
               
               
                   
               
               
                 RHHSMVYSTTSRSASLRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKARLLSIEEA 
               
               
                   
               
               
                 CKLTPPHSAKSKFGYGAKDVRSLSSRAVNHIRSVWEDLLEDTETPIDTTIMAKNEVF 
               
               
                   
               
               
                 CVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVSTLPQAVMGPSYGFQYSPGQRVE 
               
               
                   
               
               
                 FLVNTWKSKKCPMGFSYDTRCFDSTVTENDIRTEESIYQCCDLAPEARQAIRSLTER 
               
               
                   
               
               
                 LYVGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKATAACRAAKLQDCTMLVN 
               
               
                   
               
               
                 GDDLVVICESAGTQEDAAALRAFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVA 
               
               
                   
               
               
                 HDASGKRVYYLTRDPTTPLARAAWETVRHTPVNSWLGNIIMYAPTLWARMILMTHFF 
               
               
                   
               
               
                 SILLAQEQLEKALDCQIYGACYSIEPLDLPQIIERLHGLSAFSLHSYSPGEINRVAS 
               
               
                   
               
               
                 CLRKLGVPPLRVWRHRARSVRAKLLSQGGRAATCGKYLFNWAVKTKLKLTPIPAASQ 
               
               
                   
               
               
                 LDLSGWFVAGYNGGDIYHSLSRARPRWFMLCLLLLSVGVGIYLLPNR). 
               
            
           
         
       
     
     The sequences of SEQ ID NOS: 45 to 83 are sequences consisting of 9 amino acid residues contained in the full-length sequence of a certain genome protein of the HCV D89815 strain registered in the GenBank. Furthermore, the sequences of SEQ ID NOS: 45 to 83 are sequences having superior binding to an HLA-A24 type molecule as predicted by a hypothesis obtained by the experimental design method explained in Embodiment 1. SEQ ID NOS: 45 to 83 are arranged in decreasing binding order. That is, SEQ ID NO: 45 is the sequence that is predicted to have the best binding. The full-length amino acid sequence of the certain genome protein of the HCV D89815 strain is shown in SEQ ID NO: 185 
     
       
         
           
               
               
            
               
                 (MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERS 
                   
               
               
                   
               
               
                 QPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGLGWAGWLLSPRGSRPSWGPNDPR 
               
               
                   
               
               
                 RRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLP 
               
               
                   
               
               
                 GCSFSIFLLALLSCLTIPASAYEVRNVSGIYHVTNDCSNSSIVYEAADVIMHAPGCV 
               
               
                   
               
               
                 PCVRENNSSRCWVALTPTLAARNASVPTTTLRRHVDLLVGTAAFCSAMYVGDLCGSV 
               
               
                   
               
               
                 FLISQLFTFSPRRHETVQDCNCSIYPGHVSGHRMAWDMMMNWSPTAALVVSQLLRIP 
               
               
                   
               
               
                 QAVMDMVAGAHWGVLAGLAYYSMVGNWAKVLIVMLLFAGVDGHTRVTGGVQGHVTST 
               
               
                   
               
               
                 LTSLFRPGASQKIQLVNTNGSWHINRTALNCNDSLKTGFLAALFYTHKFNASGCPER 
               
               
                   
               
               
                 MASCRSIDKFDQGWGPITYAQPDNSDQRPYCWHYAPRQCGIVPASQVCGPVYCFTPS 
               
               
                   
               
               
                 PVVVGTTDRFGAPTYNWGDNETDVLLLNNTRPPHGNWFGCTWMNSTGFTKTCGGPPC 
               
               
                   
               
               
                 NIRGVGNNTLTCPTDCFRKHPDATYTKCGSGPWLTPRCLVDYPYRLWHYPCTVNFTI 
               
               
                   
               
               
                 FKVRMYVGGVEHRLDAACNWTRGERCDLEDRDRAELSPLLLSTTEWQILPCSYTTLP 
               
               
                   
               
               
                 ALSTGLIHLHQNIVDIQYLYGIGSAVVSIAIKWEYVVLLFLLLADARVCACLWMMLL 
               
               
                   
               
               
                 IAQAEAALENLVVLNAASVVGAHGMLPFFMFFCAAWYMKGRLVPGAAYAFYGVWPLL 
               
               
                   
               
               
                 LLLLALPPRAYAMDREMVASCGGGVFVGLALLTLSPYCKVFLARLIWWLQYFITKAE 
               
               
                   
               
               
                 AHLQVSLPPLNVRGGRDAIILLMCAVHPELIFDITKLLLSILGPLMVLQASLIRVPY 
               
               
                   
               
               
                 FVRAQGLIRACMLVRKAAGGHYVQMAFVKLAALTGTYVYDHLTPLQDWAHVGLRDLA 
               
               
                   
               
               
                 VAVEPVVFSAMETKVITWGADTAACGDIISGLPVSARRGKEILLGPADSFEGQGWRL 
               
               
                   
               
               
                 LAPITAYSQQTRGLLGCIITSLTGRDKNQVEGEVQVVSTAKQSFLATCVNGACWTVF 
               
               
                   
               
               
                 HGAGSKTLAAAKGPITQMYTNVDQDLVGWPAPPGARSLTPCTCGSSDLYLVTRHADV 
               
               
                   
               
               
                 IPVRRRGDSRGSLLSPRPISYLKGSSGGPLLCPSGHVVGIFRAAVCTRGVAKAVDFI 
               
               
                   
               
               
                 PVESMETTMRSPVFTDNSTPPAVPQTFQVAHLHAPTGSGKSTKVPAAYAAQGYMVLV 
               
               
                   
               
               
                 LNPSVAATLGFGAYMSKAHGIDPNIRTGVRTITTGAPITYSTYGKFLADGGCSGGAY 
               
               
                   
               
               
                 DIIICDECHSTDSTSILGIGTVLDQAETVGARFVVLATATPPGSITFPHPNIEEVPL 
               
               
                   
               
               
                 ANTGEIPFYAKTIPIEVIRGGRHLIFCHSKKKCDELPAKLSALGLNAVAYYRGLDVS 
               
               
                   
               
               
                 VIPASGDVVVVATDALMTGFTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTVPQDA 
               
               
                   
               
               
                 VSRTQRRGRTGRGRRGIYRFVTPGERPSAMFDSSVLCECYDAGCAWYELTPAETSVR 
               
               
                   
               
               
                 LRAYLNTPGLPVCQDHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCA 
               
               
                   
               
               
                 RAKAPPPSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMACMSAD 
               
               
                   
               
               
                 LEVVTSTWVLVGGVLAALAAYCLTTGSVVIVGRIILSGRPAVIPDREVLYQEFDEME 
               
               
                   
               
               
                 ECASHLPYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPVVESKWRALETFWAKHMW 
               
               
                   
               
               
                 NFISGIQYLAGLSTLPGNPAIASLMAFTASITSPLATQYTLLFNILGGWVAAQLAPP 
               
               
                   
               
               
                 SAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKVMSGDMPSTEDLV 
               
               
                   
               
               
                 NLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPE 
               
               
                   
               
               
                 SDAAARVTQILSNLTITQLLKRLHQWINEDCSTPCSGSWLRDVWDWICTVLADFKTW 
               
               
                   
               
               
                 LQSKLLPRLPGVPFFSCQRGYKGVWRGDGIMYTTCPCGAQITGHVKNGSMRIVGPRT 
               
               
                   
               
               
                 CSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAEEYVEVTRVGDFHYVTGMTTD 
               
               
                   
               
               
                 NVKCPCQVPAPEFFTELDGVRLHRYAPACKPLLRDEVTFQVGLNQYTVGSQLPCEPE 
               
               
                   
               
               
                 PDVTVVTSMLTDPSHITAEAARRRLARGSPPSLAGSSASQLSALSLKATCTTHHGAP 
               
               
                   
               
               
                 DTDLIEANLLWRQEMGGNITRVESENKIVILDSFEPLRAEEDEREVSAAAEILRKTR 
               
               
                   
               
               
                 KFPAAMPVWARPDYNPPLLESWKNPDYVPPVVHGCPLPPTKAPPIPPPRRKRTVVLT 
               
               
                   
               
               
                 ESTVSSALAELATKTFGGSGSSAVDSGTATGPPDQASAEGDAGSDAESYSSMPPLEG 
               
               
                   
               
               
                 EPGDPDLSDGSWSTVSEEASEDVVCCSMSYTWTGALITPCAAEESKLPINALSNPLL 
               
               
                   
               
               
                 RHHNMVYSTTSRSASLRQKKVTFDRMQVLDDHYRDVLKEMKAKASTVKAKLLSVEEA 
               
               
                   
               
               
                 CKLTPPHSAKSKFGYGAKDVRSLSSRAVNHIRSVWKDLLEDTDTPIQTTIMAKNEVF 
               
               
                   
               
               
                 CVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVSTLPQAVMGSSYGFQYSPKQRVE 
               
               
                   
               
               
                 FLVNTWKAKKCPMGFSYDTRCFDSTVTENDIRVEESIYQCCDLAPEARQAIRSLTER 
               
               
                   
               
               
                 LYIGGPMTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKAAAACRAAKLQDCTMLVC 
               
               
                   
               
               
                 GDDLVVICDSAGTQEDAASLRVFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVA 
               
               
                   
               
               
                 HDASGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMYAPTLWARMILMTHFF 
               
               
                   
               
               
                 SILLAQEQLEKALDCQIYGATYSIEPLDLPQIIQRLHGLSAFSLHSYSPGEINRVAS 
               
               
                   
               
               
                 CLRKLGVPPLRVWRHRARSVRAKLLSQGGRAATCGKYLFNWAVKTKLKLTPIPEASQ 
               
               
                   
               
               
                 LDLSGWFVAGYSGGDIYHSLSRARPRWFMWCLLLLSVGVGIYLLPNR). 
               
            
           
         
       
     
     The sequences of SEQ ID NOS: 84 to 123 are sequences consisting of 9 amino acid residues contained in a certain genome protein of the HCV pBRT703′X strain (mutant subclone of D89815), obtained from Professor Yoshiharu Matsuura, at the research institute for Microbial diseases at Osaka University. Furthermore, the sequences of SEQ ID NOS: 84 to 123 are sequences having superior binding to an HLA-A24 type molecule as predicted by a hypotheses obtained by the experimental design method explained in Embodiment 1. SEQ ID NOS: 84 to 123 are arranged in decreasing binding order. That is, SEQ ID NO: 84 is the sequence that is predicted to have the best binding. The full-length amino acid sequence of the certain genome protein of the HCV pBRT703′X strain (mutant subclone of D89815) is shown in SEQ ID NO: 186 
     
       
         
           
               
               
            
               
                 (MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERS 
                   
               
               
                   
               
               
                 QPRGRRQPIPKARHPEGRAWAQPGYPWPLYGNEGMGWAGWLLSPRGSRPSWGPTDPR 
               
               
                   
               
               
                 RRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLP 
               
               
                   
               
               
                 GCSFSIFLLALLSCLTIPASAYEVRNVSGIYHVTNDCSNSSIVYEAADVIMHAPGCV 
               
               
                   
               
               
                 PCVRENNSSRCWVALTPTLAARNASVPTTTLRRHVDLLVGTAAFCSAMYVGDLCGSV 
               
               
                   
               
               
                 FLISQLFTFSPRRHETVQDCNCSIYPGHVSGHRMAWDMMMNWSPTAALVVSQLLRIP 
               
               
                   
               
               
                 QAVMDMVAGAHWGVLAGLAYYSMVGNWAKVLIVMLLFAGVDGHTRVTGGVQGHVTST 
               
               
                   
               
               
                 LTSLFRPGASQKIQLVNTNGSWHINRTALNCNDSLKTGFLAALFYTHKFNASGCPER 
               
               
                   
               
               
                 MASCRSIDKFDQGWGPITYAQPDNSDQRPYCWHYAPRQCGIVPASQVCGPVYCFTPS 
               
               
                   
               
               
                 PVVVGTTDRFGAPTYNWGDNETDVLLLNNTRPPHGNWFGCTWMNSTGFTKTCGGPPC 
               
               
                   
               
               
                 NIRGVGNNTLTCPTDCFRKHPDATYTKCGSGPWLTPRCLVDYPYRLWHYPCTVNFTI 
               
               
                   
               
               
                 FKVRMYVGGVEHRLDAACNWTRGERCDLEDRDRAELSPLLLSTTEWQILPCSYTTLP 
               
               
                   
               
               
                 ALSTGLIHLHQNIVDIQYLYGIGSAVVSIAIKWEYVVLLFLLLADARVCACLWMMLL 
               
               
                   
               
               
                 IAQAEAALENLVVLNAASVAGAHGILPFFMFFCAAWYMKGRLVPGAAYAFYGVWPLL 
               
               
                   
               
               
                 LLLLALPPRAYAMDREMAASCGGGVFVGLALLTLSPYCKVFLARLIWWLQYFITKAE 
               
               
                   
               
               
                 AHLQVWVPPLNVRAGRDAIILLMCAVHPELIFDITKLLLSILGPLMVLQASLIRVPY 
               
               
                   
               
               
                 FVRAQGLIRACTLVRKAAGGHYVQMAFVKLAALTGTYVYDHLTPLQDWAHVGLRDLA 
               
               
                   
               
               
                 VAVEPVVFSAMETKVITWGADTAACGDIISGLPVSARRGKEILLGPADSFEGQGWRL 
               
               
                   
               
               
                 LAPITAYSQQTRGLLGCIITSLTGRDKNQVEGEVQVVSTATQSFLATCVNGACWTVF 
               
               
                   
               
               
                 HGAGSKTLAGPKGPITQMYTNVDQDLVGWPAPPGARSLTPCTCGSSDLYLVTRHADV 
               
               
                   
               
               
                 IPVRRRGDTRGSLLSPRPISYLKGSSGGPLLCPSGHVVGIFRAAVCTRGVAKAVDFI 
               
               
                   
               
               
                 PVESMETTMRSPVFTDNSTPPAVPQTFQVAHLHAPTGSGKSTKVPAAYAAQGYMVLV 
               
               
                   
               
               
                 LNPSVAATLGFGAYMSKAHGIDPNIRTGVRTITTGAPITYSTYGKFLADGGCSGGAY 
               
               
                   
               
               
                 DIIICDECHSTDSTSILGIGTVLDQAETAGARLVVLATATPPGSVTFPHPNIEEVAL 
               
               
                   
               
               
                 GNTGEIPFYGKAIPIEVIKGGRHLIFCHSKKKCDELAAKLSPLGLNAVAYYRGLDVS 
               
               
                   
               
               
                 VIPASGDVVVVATDALMTGFTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTVPQDA 
               
               
                   
               
               
                 VSRTQRRGRTGRGRRGIYRFVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVR 
               
               
                   
               
               
                 LRAYLNTPGLPVCQDHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCA 
               
               
                   
               
               
                 RAKAPPPSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKFIMACMSAD 
               
               
                   
               
               
                 LEVVTSTWVLVGGVLAALAAYCLTTGSVVIVGRIILSGRPAVIPDREVLYQEFDEME 
               
               
                   
               
               
                 ECASHLPYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPVVESKWRALETFWAKHMW 
               
               
                   
               
               
                 NFISGIQYLAGLSTLPGNPAIASLMAFTASITSPLATQYTLLFNILGGWVAAQLAPP 
               
               
                   
               
               
                 SAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKVMSGDMPSTEDLV 
               
               
                   
               
               
                 NLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPE 
               
               
                   
               
               
                 SDAAARVTQILSNLTITQLLKRLHQWINEDCSTPCSGSWLRDVWDWICTVLADFKTW 
               
               
                   
               
               
                 LQSKLLPRLPGVPFFSCQRGYKGVWRGDGIMYTTCPCGAQITGHVKNGSMRIVGPRT 
               
               
                   
               
               
                 CSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAEEYVEVTRVGDFHYVTGMTTD 
               
               
                   
               
               
                 NVKCPCQVPAPEFFTELDGVRLHRYAPACKPLLRDEVTFQVGLNQYTVGSQLPCEPE 
               
               
                   
               
               
                 PDVTVVTSMLTDPSHITAEAARRRLARGSPPSLAGSSASQLSAPSLKATCTTHHGAP 
               
               
                   
               
               
                 DTDLIEANLLWRQEMGGNITRVESENKIVILDSFEPLRAEEDEREVSAAAEILRKTR 
               
               
                   
               
               
                 KFPAAMPVWARPDYNPPLLESWKNPDYVPPVVHGCPLPPTKAPPIPPPRRKRTVVLT 
               
               
                   
               
               
                 ESTVSSALAELATKTFGGSGSSAVDSGTATGPPDQASAEGDAGSDAESYSSMPPLEG 
               
               
                   
               
               
                 EPGDPDLSDGSWSTVSEEASEDVVCCSMSYTWTGALITPCAAEESKLPINALSNPLL 
               
               
                   
               
               
                 RHHNMVYSTTSRSASLRQKKVTFDRMQVLDDHYRDVLKEMKAKASTVKAKLLSVEEA 
               
               
                   
               
               
                 CKLTPPHSAKSKFGYGAKDVRSLSSRAVNHIRSVWKDLLEDTDTPIQTTIMAKNEVF 
               
               
                   
               
               
                 CVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVSTLPQAVMGSSYGFQYSPKQRVE 
               
               
                   
               
               
                 FLVNTWKAKKCPMGFSYDTRCFDSTVTENDIRVEESIYQCCDLAPEARQAIRSLTER 
               
               
                   
               
               
                 LYIGGPMTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKAAAACRAAKLQDCTMLVC 
               
               
                   
               
               
                 GDDLVVICDSAGTQEDAASLRVFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVA 
               
               
                   
               
               
                 HDASGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMYAPTLWARMILMTHFF 
               
               
                   
               
               
                 SILLAQEQLEKALDCQIYGATYSIEPLDLPQIIQRLHGLSAFSLHSYSPGEINRVAS 
               
               
                   
               
               
                 CLRKLGVPPLRVWRHRARSVRAKLLSQGGRAATCGKYLFNWAVKTKLKLTPIPEASQ 
               
               
                   
               
               
                 LDLSGWFVAGYSGGDIYHSLSRARPRWFMWCLLLLSVGVGIYLLPNR). 
               
            
           
         
       
     
     The sequences of SEQ ID NOS: 124 to 183 are sequences consisting of 9 amino acid residues contained in a certain genome protein of the above-mentioned HCV pBRT703′X strain (mutant subclone of D89815). Furthermore, the sequences of SEQ ID NOS: 124 to 183 are sequences having superior binding to an HLA-A2 type molecule as predicted by a hypotheses obtained by the experimental design method explained in Embodiment 1. SEQ ID NOS: 124 to 183 are arranged in decreasing binding order. That is, SEQ ID NO: 124 is the sequence that is predicted to have the best binding. 
     Table 1 to Table 4 show amino acid sequences that had superior scores in the predicted results obtained using the above-mentioned prediction program, the predicted score, and the corresponding binding experiment data for the HCV D90208 strain, the D89815 strain, and the pBRT703′X strain (mutant subclone of D89815). All of the binding experiment data were obtained by artificially synthesizing 9 amino acid peptides by the above-mentioned synthetic method. 
     Said certain genome proteins of the HCV D90208 strain and the D89815 strain are registered in the GenBank, but the sequences consisting of 9 amino acid residues therein, which are the HLA-binding peptides, are not currently registered. 
     Furthermore, the pBRT703′X strain (mutant subclone of D89815) is a mutant strain that is similar to a substrain of HCV often seen in Japanese hepatitis C patients. In the present example, an HLA-binding peptide contained in a certain genome protein of the mutant strain similar to the substrain often seen in Japanese people has been found. This HLA-binding peptide can suitably be used for the development of a hepatitis C therapeutic drug for Japanese people. 
     Here, the amino acid sequences of the certain genome proteins of the above-mentioned HCV D90208 strain, D89815 strain, and pBRT703′X strain (mutant subclone of D89815) are different from each other in part, and it can be predicted that even an amino acid sequence formed by substitution of one or a few amino acid residues in the amino acid sequence will similarly show excellent HLA-binding properties as described above. 
     For example, the sixth peptide from the left of SEQ ID NO: 1 of the D90208 strain is F, but it is Y for the peptide of SEQ ID NO: 46 of the D89815 strain and the peptide of SEQ ID NO: 85 of the pBRT703′X strain (mutant subclone of D89815). 
     Furthermore, the second peptide from the left of SEQ ID NO: 17 of the D90208 strain is L, but it is F for the peptide of SEQ ID NO: 49 of the D89815 strain and the peptide of SEQ ID NO: 98 of the pBRT703′X strain (mutant subclone of D89815). 
     Moreover, the fifth peptide from the left of SEQ ID NO: 3 of the D90208 strain is V, but it is A for the peptide of SEQ ID NO: 71 of the D89815 strain and the peptide of SEQ ID NO: 110 of the pBRT703′X strain (mutant subclone of D89815). 
     Furthermore, the seventh peptide from the left of SEQ ID NO: 2 of the D90208 strain is D, but it is E for the peptide of SEQ ID NO: 45 of the D89815 strain and the peptide of SEQ ID NO: 84 of the pBRT703′X strain (mutant subclone of D89815). 
     Moreover, the seventh peptide from the left of SEQ ID NO: 40 of the D90208 strain is C, but it is G for the peptide of SEQ ID NO: 107 of the pBRT703′X strain (mutant subclone of D89815). 
     Furthermore, the fifth peptide from the left of SEQ ID NO: 43 of the D90208 strain is E, but it is D for the peptide of SEQ ID NO: 59 of the D89815 strain and the peptide of SEQ ID NO: 87 of the pBRT703′X strain (mutant subclone of D89815), and the eighth peptide from the left of SEQ ID NO: 43 of the D90208 strain is V, but it is T for the peptide of SEQ ID NO: 59 of the D89815 strain and the peptide of SEQ ID NO: 87 of the pBRT703′X strain (mutant subclone of D89815). 
     Moreover, the seventh peptide from the left of SEQ ID NO: 44 of the D90208 strain is I, but it is V for the peptide of SEQ ID NO: 62 of the D89815 strain and the peptide of SEQ ID NO: 93 of the pBRT703′X strain (mutant subclone of D89815), and the ninth peptide from the left of SEQ ID NO: 44 of the D90208 strain is V, but it is F for the peptide of SEQ ID NO: 62 of the D89815 strain and the peptide of SEQ ID NO: 93 of the pBRT703′X strain. 
     Among the peptide sequences formed by substitution of one or two amino acid residues with each other, for example, the second peptide from the left of SEQ ID NO: 17 of the D90208 strain is L, but it is F for the peptide of SEQ ID NO: 49 of the D89815 strain and the peptide of SEQ ID NO: 98 of the pBRT703′X strain (mutant subclone of D89815), and the binding experimental value for the peptide of SEQ ID NO: 17 of the D90208 strain is 6.98038 whereas it is 7.7344 for the peptide of SEQ ID NO: 49 of the D89815 strain and the peptide of SEQ ID NO: 98 of the pBRT703′X strain (mutant subclone of D89815), thus confirming that they all show good binding properties. 
     Furthermore, among the peptide sequences formed by substitution of one or two amino acid residues with each other, for example, the seventh peptide from the left of SEQ ID NO: 40 of the D90208 strain is C, but it is G for the peptide of SEQ ID NO: 107 of the pBRT703′X strain (mutant subclone of D89815), and the binding experimental value for the peptide of SEQ ID NO: 40 of the D90208 strain is 6.97507 whereas it is 6.37373 for the peptide of SEQ ID NO: 107 of the pBRT703′X strain (mutant subclone of D89815), thus confirming that they all show good binding properties. 
     Moreover, among the peptide sequences formed by substitution of one or two amino acid residues with each other, for example, the fifth peptide from the left of SEQ ID NO: 3 of the D90208 strain is V, but it is A for the peptide of SEQ ID NO: 71 of the D89815 strain and the peptide of SEQ ID NO: 110 of the pBRT703′X strain (mutant subclone of D89815), and the binding experimental value for the peptide of SEQ ID NO: 3 of the D90208 strain is 6.14848 whereas it is 6.75756 for the peptide of SEQ ID NO: 71 of the D89815 strain and the peptide of SEQ ID NO: 110 of the pBRT703′X strain (mutant subclone of D89815), thus confirming that they all show good binding properties. 
     Furthermore, among the peptide sequences formed by substitution of one or two amino acid residues with each other, for example, the seventh peptide from the left of SEQ ID NO: 2 of the D90208 strain is D, but it is E for the peptide of SEQ ID NO: 45 of the D89815 strain and the peptide of SEQ ID NO: 84 of the pBRT703′X strain (mutant subclone of D89815), and the binding experimental value for the peptide of SEQ ID NO: 2 of the D90208 strain is 5.32417 whereas it is 5.00343 for the peptide of SEQ ID NO: 45 of the D89815 strain and the peptide of SEQ ID NO: 84 of the pBRT703′X strain (mutant subclone of D89815), thus confirming that they all show good binding properties. 
     Moreover, among the peptide sequences formed by substitution of one or two amino acid residues with each other, for example, the amino acid sequence is offset sideways by one between the peptide of SEQ ID NO: 90 and the peptide of SEQ ID NO: 112 of the pBRT703′X strain (mutant subclone of D89815), and the binding experimental value for the peptide of SEQ ID NO: 90 is 6.51874 whereas the binding experimental value for the peptide of SEQ ID NO: 112 is 6.63423, thus confirming that they all show good binding properties. 
     Furthermore, among the peptide sequences formed by substitution of one or two amino acid residues with each other, for example, the amino acid sequence is offset sideways by one between the peptide of SEQ ID NO: 13 of the D90208 strain and the peptide of SEQ ID NO: 60 of the D89815 strain and the peptide of SEQ ID NO: 18 of the D90208 strain and the peptide of SEQ ID NO: 64 of the D89815 strain, and the binding experimental value for the peptides of SEQ ID NOS: 13 and 60 is 7.89519 whereas the binding experimental value for the peptides of SEQ ID NOS: 18 and 64 is 5.9169, thus confirming that they all show good binding properties. 
     It can therefore be predicted that both the peptide sequences formed by substitution of one or two amino acid residues with each other will show excellent binding to an HLA-A24 type molecule. In conclusion, even an amino acid sequence formed by deletion, substitution, or addition of one or a few amino acid residues of an amino acid sequence that has excellent properties in binding to an HLA-A type molecule shown by SEQ ID NOS: 1 to 183 can be predicted to similarly show excellent HLA-binding properties. 
     From another viewpoint, even an amino acid sequence formed by deletion, substitution, or addition of one or a few amino acid residues of an amino acid sequence that has excellent properties in binding to an HLA-A type molecule as predicted by the hypothesis obtained by the experimental design method explained in Embodiment 1 similarly can be said to show excellent HLA-binding properties. The amino acid residues that are substituted are preferably amino acid residues that have similar properties to each other, such as the two being hydrophobic amino acid residues. 
     The present invention is explained above by reference to Examples. These Examples are only illustrated as examples, and a person skilled in the art will understand that various modification examples are possible, and such modification examples are included in the scope of the present invention. 
     For example, in the above-mentioned Examples, HCV D90208 strain, D89815 strain, and pBRT703′X strain (mutant subclone of D89815) were used, but another HCV strain may be used. In this case, in accordance with the prediction program employed in the present invention, the HLA binding can be predicted with high precision.