Identification of EphB6 variant-derived epitope peptides recognized by cytotoxic T-lymphocytes from HLA-A24+ malignant glioma patients.

We found previously that EphB6, a member of the erythropoietin-producing hepatocyte (Eph) receptor tyrosine kinase family, was preferentially expressed in malignant gliomas. In the present study, RT-PCR revealed a putative secretory variant form of human EphB6 that was expressed in the majority of glioma cell lines, though not in normal tissues. The variant has a unique 54 amino acid sequence that is not found in the normal EphB6. Therefore, we attempted to determine the antigenic peptides unique to the variant for immunotherapy. The two variant-derived peptides had the ability to bind to HLA-A2402 molecules and each of them could induce cytotoxic T-lymphocytes (CTLs) in vitro in peripheral blood mononuclear cells of HLA-A24(+) glioma patients. Furthermore, the cytotoxicity was mediated by peptide-specific CD8(+) T cells in an HLA-A24 restricted manner. Taken together, the two peptides derived from the variant of EphB6 might be appropriate targets for peptide-based specific immunotherapy to HLA-A24(+) patients with malignant glioma.