Study of molecular basis for T cell-mediated recognition of antigens in subjects with HLA-A3 super type

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1. Cancer associated antigen-derived peptides: We have identified new peptides from SART3 and Lck antigens that are recognized by HLA-A3 super family-restricted cytotoxic T lymphocytes (CTL) (Minami, et. Al., Cancer Immunol. Immunoth.: Naito, et. Al., Brit.J.Can. 2007).2. Exogenous antigen-derived peptides: We have identified new peptides from hepatitis C virus sequences that are recognized by HLA-A3 super family-restricted CTL (Matsueda, et. Al., Cancer Immunol Immunotherapy, 2007). Furthermore, we found that measurement of lgG antibodies specific to core region of hepatitis C virus at positions 35-44 (C35-44) is a possible new diagnostic tool of hepatitis C virus infection (Takao, et. Al., Med. Mirobiol. Immunol., 2007).3. Self antigen-derived peptides: We have identified new peptides from self antigens that are recognized by HLA-A3 super family-restricted CTL (Matsueda, et. Al., J. Immunotherpy 2007).4. Summary: We have obtained new evidence during the past two years with regard to molecular basis of T cell-mediated recognition of antigens in both healthy donors and cancer patients belonging to HLA-A3 super type (HLA-A3,-A 11, -A31, and-A33). The binding motifs of these newly identified peptides to HLA-class IA alleles of HLA-A3 super type were mostly unpredictable from the currently available database of MHC binding peptides predicting the binding of peptides to HLA-class IA alleles of A3 super type. These results indicate that the binding motifs of CTL epitopes to HLA-class IA alleles of HLA-A3 super type are different form those expected in the past. The results created in this grant shall facilitate to better understanding of host responses to cancer cells as well as viral antigens in subjects of HLA-A3 super type, and may contribute to development of new database of MHC binding peptides.