A wild-type p53 cytotoxic T cell epitope is presented by mouse hepatocarcinoma cells.

Abstract

The possibility to identify epitopes presented by tumor cells to cytotoxic T lymphocytes (CTL) has given rise to new fields in tumor immunology. The tumor suppressor gene product p53 is a good candidate antigen because it is involved in the tumorigenesis of many cancers. It accumulates in an inactivated form due to mutation or formation of heterodimers with an oncogene product. Epitopes from the mutant or wild-type p53 proteins are thought to be presented by tumor cells and to induce a tumor-specific CTL response. To identify such epitopes, mouse wild-type p53 peptides encompassing the H-2 Db anchoring motif were tested for their association with the Db molecule. Positive peptides were assayed for their ability to induce CTL in C57BL/6 mice. CTL specific for one wild-type p53 peptide, p232-240, were isolated and found to lyse hepatocarcinoma cell lines established from mice transgenic for simian virus 40 large T antigen which overexpress p53. These results show that the p232-240 epitope from wild-type p53 is naturally processed and presented in H-2b tumor cells.