HLA binding peptides and their uses
The present invention provides the means and methods for selecting immunogenic peptides and the immunogenic peptide compositions capable of specifically binding glycoproteins encoded by HLA alleles and inducing T cell activation in T cells restricted by the allele. The peptides are useful to elicit an immune response against a desired antigen. The immunogenic peptide compositions of the present invention comprise immunogenic peptides having an HLA binding motif, where the peptide is from a target antigen. Target antigens of the present invention include prostate specific antigen (PSA), hepatitis B core and surface antigens (HBVc, HBVs) hepatitis C antigens, Epstein-Barr virus antigens, melanoma antigens (e.g., MAGE-1), human immunodeficiency virus (HIV) antigens, human papilloma virus (HPV) antigens, Lassa virus, mycobacterium tuberculosis (MT), p53, CEA, trypanosome surface antigen (TSA) and Her2/neu.
1 . A composition comprising an immunogenic peptide having an HLA-A2.1 binding motif, which immunogenic peptide is selected from a group consisting of:
AILTFGSFV,
HLRDFALAV,
ALLGSIALL,
ALLATILAA,
LLATILAAV,
RLFADELAA,
YLSKCTLAV,
LVYHIYSKI,
SMYLCILSA,
YLCILSALV,
VMFSYLQSL,
RLHVYAYSA,
GLQTLGAFV,
FVEEQMTWA,
QMTWAQTVV,
IILDTAIFV,
AIFVCNAFV,
AMGNRLVEA,
RLVEACNLL
TLSIVTFSL,
KLSVLLLEV,
LLLEVNRSV,
FVSSPTLPV,
AMLVLLAEI,
QMARLAWEA,
VLAIEGIFMA,
YLYHPLLSPI,
SLFEAMLANV,
STTGTNQLGL,
LAILTFGSFV,
ALLGSIALLA,
ALLATILAAV,
LLATILAAVA,
RLFADELAAL,
YLSKCTLAVL,
LLVYHIYSKI,
SMYLCILSAL,
HLHRQMLSFV,
LLCGKTGAFL,
ETLSIVTFSL,
VMCTYSPPL,
KLFCQLAKT,
ATPPAGSRV,
FLQSGTAKSV,
CMDRGLTVFV,
VLLNWWRWRL,
GVFTGLTHI,
QMWKCLIRL,
IMTCMSADL,
ALAAYCLST,
VLSGKPAII,
FISGIQYLA,
YIMTCMSADL,
AIASLMAFTA,
GLAGAAIGSV,
MIGVLVGV,
VLPLAYISL,
SLGCIFFPL,
PLAYISLFL,
LMLFYQVWA,
NISIYNYFV,
NISVYNYFV,
FVWTHYYSV,
FLTWHRYHL,
LTWHRYHLL,
MLQEPSFSL,
SLPYWNFAT,
RLPEPQDVA,
VTQCLEVRV,
LLHTFTDAV,
NMVPFWPPV,
AVVGALLLV,
AVVAALLLV,
LLVAAIFGV,
SMDEANQPL,
VLPLAYISV,
SLGCIFFPV,
PLAYISLFV,
LLLFQQARV,
LMLFYQVWV,
LLPSSGPGV,
NLSIYNYFV,
NLSVYNYFV,
FLWTHYYSV,
SLKKTFLGV,
FLTWHRYHV,
MLQEPSFSV,
SLPYWNFAV,
ALGKNVCDV,
SLLISPNSV,
SLFSQWRVV,
TLGTLCNSV,
RLPEPQDVV,
VLQCLEVRV,
SLNSFRNTV,
SLDSFRNTV
FLNGTGGQV
VLLHTFTDV
ALVGALLLV
ALVAALLLV,
LLVALIFGV,
YLIRARRSV,
SMDEANQPV,
SLGCIFFPLL,
GMCCPDLSPV,
AACNQKILTV
FLTWHRYHLL,
SLHNLAHLFL
LLLVAAIFGV
LLVAAIFGVA,
ALIFGTASYL,
SMDEANQPLL,
LLTDQYQCYA,
SLGCIFFPLV,
FLMLFYQVWV,
ALCDQRVLIV,
ALCNQKILTV,
FLTWHRYHLV,
SLHNLAHLFV,
NLAHLFLNGV,
NMVPFWPPVV,
ILVVAALLLV,
LLVALIFGTV,
ALIFGTASYV,
SMDEANQPLV,
LLTDQYQCYV,
LLIQNIIQNDT,
IIQNDTGFYTL,
TLFNVTRNDTA
LTLLSVTRNDV
GLYTCQANNSA,
ATVGIMIGVLV,
GLVPPQHLIRV,
GLAPPVHLIRV,
GLAPPEHLIRV,
ILIGVLVGV,
YLIMVKCWMV,
LLGRDSFEV,
FMYSDFHFI,
NMLSTVLGV
SLENFRAYV,
KMAELVHFV,
KLAELVHFV
VLIQRNPQV,
VLLGVVFGV,
SLISAVVGV,
YMIMVKBWMI,
YLIMVKBWMV,
KLWEELSVV,
AMBRWGLLV,
IJIGVLVGV,
ATVGIJIGV,
SJPPPGTRV,
LVFGIELJEV,
ILGFVFTL,
KIFGSLAFL,
YLQLVFGIEV,
MMNDQLMFL,
ALVLAGGFFL,
WLCAGALVL,
MVFELANSI,
RMMNDQLMFL,
LVLAGGFFL,
VLAGGFFLL,
LLHETDSAV,
LMYSLVHNL,
QLMFLERAFI,
LMFLERAFI,
KLGSGNDFEV,
LLQERGVAYI,
GMPEGDLVYV,
FLDELKAENI,
ALFDIESKV,
and
GLPSIPVHPI.
2 . A method of inducing a cytotoxic T cell response against a preselected antigen in a patient expressing an HLA-A2.1 MHC product, the method comprising contacting cytotoxic T cells from the patient with a composition comprising an immunogenic peptide selected from the group consisting of:
AILTFGSFV,
HLRDFALAV,
ALLGSIALL,
ALLATILAA,
LLATILAAV,
RLFADELAA,
YLSKCTLAV,
LVYHIYSKI,
SMYLCILSA,
YLCILSALV,
VMFSYLQSL,
RLHVYAYSA,
GLQTLGAFV,
FVEEQMTWA,
QMTWAQTVV,
IILDTAIFV,
AIFVCNAFV,
AMGNRLVEA,
RLVEACNLL
TLSIVTFSL,
KLSVLLLEV,
LLLEVNRSV,
FVSSPTLPV,
AMLVLLAEI,
QMARLAWEA,
VLAIEGIFMA,
YLYHPLLSPI,
SLFEAMLANV,
STTGINQLGL,
LAILTFGSFV,
ALLGSIALLA,
ALLATILAAV,
LLATILAAVA,
RLFADELAAL,
YLSKCTLAVL,
LLVYHIYSKI,
SMYLCILSAL,
HLHRQMLSFV,
LLCGKTGAFL,
ETLSIVTFSL,
VMCTYSPPL,
KLFCQLAKT,
ATPPAGSRV,
FLQSGTAKSV,
CMDRGLTVFV,
VLLNWWRWRL,
GVFTGLTHI,
QMWKCLIRL,
IMTCMSADL,
ALAAYCLST,
VLSGKPAII,
FISGIQYLA,
YIMTCMSADL,
AIASLMAFTA,
GLAGAAIGSV,
MIGVLVGV,
VLPLAYISL,
SLGCIFFPL,
PLAYISLFL,
LMLFYQVWA,
NISIYNYFV,
NISVYNYFV,
FVWTHYYSV,
FLTWHRYHL,
LTWHRYHLL,
MLQEPSFSL,
SLPYWNFAT,
RLPEPQDVA,
VTQCLEVRV,
LLHTFTDAV,
NMVPFWPPV,
AVVGALLLV,
AVVAALLLV,
LLVAAIFGV,
SMDEANQPL,
VLPLAYISV,
SLGCIFFPV,
PLAYISLFV,
LLLFQQARV,
LMLFYQVWV,
LLPSSGPGV,
NLSIYNYFV,
NLSVYNYFV,
FLWTHYYSV,
SLKKTFLGV,
FLTWHRYHV,
MLQEPSFSV,
SLPYWNFAV,
ALGKNVCDV,
SLLISPNSV,
SLFSQWRVV,
TLGTLCNSV,
RLPEPQDVV,
VLQCLEVRV,
SLNSFRNTV,
SLDSFRNTV
FLNGTGGQV
VLLHTFTDV
ALVGALLLV
ALVAALLLV,
LLVALIFGV,
YLIRARRSV,
SMDEANQPV,
SLGCIFFPLL,
GMCCPDLSPV,
AACNQKILTV
FLTWHRYHLL,
SLHNLAHLFL
LLLVAAIFGV
LLVAAIFGVA,
ALIFGTASYL,
SMDEANQPLL,
LLTDQYQCYA,
SLGCIFFPLV,
FLMLFYQVWV,
ALCDQRVLIV,
ALCNQKILTV,
FLTWHRYHLV,
SLHNLAHLFV,
NLALHLFLNGV,
NMVPFWPPVV,
ILVVAALLLV,
LLVALIFGTV,
ALIFGTASYV,
SMDEANQPLV,
LLTDQYQCYV,
LLIQNIIQNDT,
IIQNDTGFYTL,
TLFNVTRNDTA
LTLLSVTRNDV
GLYTCQANNSA,
ATVGIMIGVLV,
GLVPPQHLIRV,
GLAPPVHLIRV,
GLAPPEHLIRV,
ILIGVLVGV,
YLIMVKCWMV,
LLGRDSFEV,
FMYSDFHFI,
NMLSTVLGV
SLENFRAYV,
KMAELVHFV,
KLAELVHFV
VLIQRNPQV,
VLLGVVFGV,
SLISAVVGV,
YMIMVKBWMI,
YLIMVKBWMV,
KLWEELSVV,
AMBRWGLLV,
IJIGVLVGV,
ATVGIJIGV,
SJPPPGTRV,
LVFGIELJEV,
ILGFVFTL,
KIFGSLAFL,
YLQLVFGIEV,
MMNDQLMFL,
ALVLAGGFFL,
WLCAGALVL,
MVFELANSI,
RMMNDQLMFL,
LVLAGGFFL,
VLAGGFFLL,
LLHETDSAV,
LMYSLVHNL,
QLMFLERAFI,
LMFLERAFI,
KLGSGNDFEV,
LLQERGVAYI,
GMPEGDLVYV,
FLDELKAENI,
ALFDIESKV,
and
GLPSIPVHPI.
3 . A composition comprising an immunogenic peptide selected from a group consisting of:
RVYPELPK,
TVSAELPK,
TVYAEPPK,
TINYTLWR,
LVHFLLLK,
SVFAHPRK,
KVLHHMVK,
RVCACPGR,
KMFCQLAK,
RAHSSHLK,
FVSNLATGR,
RLQLSNGNK,
RINGIPQQK,
KIRKYTMRK,
LVHFLLLKK,
SMLEVFEGK,
SSFSTTINK,
TSYVKVLHK,
VIFSKASEK,
GSVVGNWQK,
SSLPTTMNK,
SVLEVFEGK,
SSBMGGMNK,
SSCMGGMNK,
RTLTLFNVTK,
TISPLNTSYK,
STTINYTLWK,
ASSLPTTMNK,
KTYQGSYGFK,
VVRRBPHHEK,
GLAPPQHLIK,
NSSCMGGMNK,
SSBMGGMNRK,
RVCACPGRDK,
KTITVSAELPK,
TTITVYAEPPK,
PTISPSYTYYR,
GLLGDNQVMPK,
MVELVHFLLLK,
FSTTINYTLWR,
GLLGDNQIMPK,
RLGFLHSGTAK,
ALNKMFCQLAK,
RVCACPGRDRR,
LSQETFSDLWK,
RAHSSHLKSKK,
VTCTYSPALNK,
GTRVRAMAIYK,
STSRHKKLMFK,
LAARNVLVK,
MALESILRR,
ISWLGLRSLR,
GSGAFGTVYK,
and
ASPLDSTFYR.
4 . A method of inducing a cytotoxic T cell response against a preselected antigen in a patient, the method comprising contacting cytotoxic T cells from the patient with a composition comprising an immunogenic peptide selected from the group consisting of:
RVYPELPK,
TVSAELPK,
TVYAEPPK,
TINYTLWR,
LVHFLLLK,
SVFAHPRK,
KVLHHMVK,
RVCACPGR,
KMFCQLAK,
RAHSSHLK,
FVSNLATGR,
RLQLSNGNK,
RINGIPQQK,
KIRKYTMRK,
LVHFLLLKK,
SMLEVFEGK,
SSFSTTINK,
TSYVKVLHK,
VIFSKASEK,
GSVVGNWQK,
SSLPTTMNK,
SVLEVFEGK,
SSBMGGMNK,
SSCMGGMNK,
RTLTLFNVTK,
TISPLNTSYK,
STTINYTLWK,
ASSLPTTMNK,
KTYQGSYGFK,
VVRRBPHHEK,
GLAPPQHLIK,
NSSCMGGMNK,
SSBMGGMNRK,
RVCACPGRDK,
KTITVSAELPK,
TTITVYAEPPK,
PTISPSYTYYR,
GLLGDNQVMPK,
MVELVHFLLLK,
FSTTINYTLWR,
GLLGDNQIMPK,
RLGFLHSGTAK,
ALNKMFCQLAK,
RVCACPGRDRR,
LSQETFSDLWK,
RAHSSHLKSKK,
VTCTYSPALNK,
GTRVRAMAIYK,
STSRHKKLMFK,
LAARNVLVK,
MALESILRR,
ISWLGLRSLR,
GSGAFGTVYK,
and
ASPLDSTFYR.
5 . A composition comprising an immunogenic peptide selected from a group consisting of the peptides listed in Tables 3, 12 and 13.
6 . A method of inducing a cytotoxic T cell response against a preselected antigen in a patient, the method comprising contacting cytotoxic T cells from the patient with a composition comprising an immunogenic peptide selected from the group consisting of the peptides listed in Tables 3, 12 and 13.
7 . A composition comprising an immunogenic peptide, wherein said immunogenic peptide consists of a sequence selected from a group consisting of SEQ ID NOs: 1-377.
8 . A composition comprising an immunogenic peptide of less than about 15 amino acids in length, wherein said immunogenic peptide comprises a sequence selected from the group consisting of SEQ ID NOs: 1-377.
9 . An isolated peptide less than about 15 amino acids in length, wherein said peptide comprises a sequence selected from the group consisting of SEQ ID NOs: 1-377.
10 . An isolated peptide having a sequence selected from a group consisting of SEQ ID NOs: 1-377.
11 . A method of inducing a cytotoxic T cell response against a preselected antigen in a patient, comprising contacting cytotoxic T cells from the patient with the composition of claim 7 or 8 .
12 . The composition of claim 7 , wherein said immunogenic peptide comprises the sequence KLBPVQLWV (SEQ ID NO:9).
13 . The composition of claim 8 , wherein said immunogenic peptide comprises the sequence KLBPVQLWV (SEQ ID NO:9).
14 . The isolated peptide of claim 9 , wherein said peptide comprises the sequence KLBPVQLWV (SEQ ID NO:9).
15 . The isolated peptide of claim 10 , wherein said peptide consists of the sequence KLBPVQLWV (SEQ ID NO:9).
16 . The composition of claim 7 , wherein said immunogenic peptide comprises the sequence SMPPPGTRV (SEQ ID NO:4).
17 . The composition of claim 8 , wherein said immunogenic peptide comprises the sequence SMPPPGTRV (SEQ ID NO:4).
18 . The isolated peptide of claim 9 , wherein said peptide comprises the sequence SMPPPGTRV (SEQ ID NO:4).
19 . The isolated peptide of claim 10 , wherein said peptide consists of the sequence SMPPPGTRV (SEQ ID NO:4).