A cyclophilin B gene encodes antigenic epitopes recognized by HLA-A24-restricted and tumor-specific CTLs

We have studied Ags recognized by HLA class I-restricted CTLs established f rom tumor site to better understand the molecular basis of tumor immunology , HLA-A24-restricted and tumor-specific CTLs established from T cells infil trating into lung adenocarcinoma recognized the two antigenic peptides enco ded by a cyclophilin B gene, a family of genes for cyclophilins involved in T cell activation. These two cyclophilin B peptides at positions 84-92 and 91-99 induced HLA-A24-restricted CTI, activity against tumor cells in PBMC s of leukemia patients, but not in epithelial cancer patients or in healthy donors. In contrast, the modified peptides at position 2 from phenylalanin e to tyrosine, which had more than 10 times higher binding affinities to HL A-A24 molecules, could induce HLA-A24-restricted CTL activity against tumor cells In PBMCs from leukemia patients, epithelial cancer patients, or heal thy donors, PHA-activated normal T cells were resistant to lysis by the CTL line or by these peptide-induced CTLs. These results indicate that a cyclo philin B gene encodes antigenic epitopes recognized by CTLs at the tumor si te, although T cells in peripheral blood (except for those from leukemia pa tients) are immunologically tolerant to the cyclophilin B. These peptides m ight be applicable for use in specific immunotherapy of leukemia patients o r that of epithelial cancer patients.