Mapping of H–2 genes associated with T cell-mediated cytotoxic responses to SV40–tumour-associated specific antigens

Abstract

T CELL-MEDIATED cytotoxic responses to cells carrying viral antigens¹, haptens² and male H–Y antigen³, as well as minor histocompatibility antigens⁴ are known to be associated with either the K or D region of the murine major histocompatibility complex (H–2). Similarly, T cell-mediated cytolysis of SV40-transformed cells expressing tumour-associated specific antigens (TASA) is restricted to syngeneic target cells^5–8. Although good cytotoxic responses to SV40-transformed cells can be found in mice of H–2^b haplotype after primary in vivo immunisation⁵, the response of mice of other H–2 haplotypes is quite poor (unpublished observations), but can be readily demonstrated after in vitro^6–8 mixed cell cultures. We demonstrate here primary cytotoxic responses to SV40–TASA in various inbred mouse strains using an immunisation protocol previously applied to the primary in vivo induction of hapten-specific⁹ and virus-specific cytotoxic T lymphocytes (CTL)¹⁰. Moreover, the availability of appropriate congeneic recombinant mice as responders and SV40-transformed cells from these mouse strains as target cells, has enabled us to map the anti-SV40–TASA response within the H–2 complex. The data establish that the response is restricted to H–2K or H–2D, and indicate the existence of a possible Ir gene influence on the T-cell response to SV40–TASA associated with H–2D^d.