Mouse tumors induced with chemical carcinogens or UV light are immunogenic: Tumor cells killed by irradiation or living tumor cells later removed by surgery confer to the inoculated animal a lasting protection against a challenge with the same tumor cells (Klein et al. 1960; Kripke and Fisher 1976). This specific protection was the first evidence for the existence of specific tumor rejection antigens. T lymphocytes were shown to carry the specific memory involved in these responses. Later, it became apparent that many tumors, including most, if not all, spontaneous tumors, do not elicit any immune rejection response (Hewitt et al. 1976). However, from such nonimmunogenic tumor cell lines that were treated in vitro with a mutagen, it was possible to derive variants that expressed potent new antigens (Van Pel et al. 1983). These" turn-" variants were rejected by syngeneic mice, and these mice were protected against a challenge with the original tumor cells, indicating that, even though they are not immunogenic, these tumors also carry tumor rejection antigens that can constitute targets for immune rejection responses. These results suggested that most, if not all, mouse tumors bear antigens that can be targets for immune rejection mediated by syngeneic T lymphocytes. They also indicated that tumor antigens that do not elicit any immune response can be made to do so by artificial means.

Antigens recognized by T lymphocytes are small peptides inserted in a groove of major histocompatibility complex (MHC) molecules (Townsend et al. 1986; Bjorkman et al. 1987). Peptides derived from exogenous proteins captured by cells are presented by class II MHC molecules and are recognized by CD4+ T lymphocytes. Peptides derived from proteins synthesized inside the cell are predominantly presented by class I MHC molecules and are recognized by CD8+ T lymphocytes, but some of these endogenous peptides appear to be presented by class II MHC molecules to CD4 § T lymphocytes.