Serine Proteinase Inhibitor 9 Can Be Recognized by Cytotoxic T Lymphocytes of Epithelial Cancer Patients

摘要

Serine proteinase inhibitor 9 (PI–9) inhibits granzyme B‐mediated apoptosis and interleukin–lβ‐converting enzyme activity. In this study, we report that the PI–9 gene encodes antigenic epitopes recognized by the HLA‐A24–restricted and tumor‐reactive cytotoxic T lymphocytes (CTLs) of epithelial cancer patients. Screening of an autologous cDNA library using a CTL line recognizing HLA‐A24⁺ tumor cells resulted in the isolation of a cDNA, which had an identical coding region to the previously described PI–9 genes. PI–9 gene was expressed in approximately three‐fourths of epithelial cancer cell lines and all leukemic cell lines tested. It was also expressed in normal peripheral blood mononuclear cells (PBMCs), but not in a normal fibroblast cell line. CTL sublines contained T cells capable of recognizing the PI–9292–300 and PI–9348–356 peptides among 13 different peptides having the HLA‐A24 binding motifs. These two peptides were recognized by the CTL line in a dose‐dependent and HLA class‐I‐restricted manner, and also possessed the ability to induce HLA class I‐restricted and tumor‐reactive CTLs in PBMCs from HLA‐A24⁺ cancer patients. These results demonstrate that PI–9 is recognized by HLA class I‐restricted and tumor‐reactive CTLs of epithelial cancer patients.