Genetic Control of the Cytotoxic T Cell Response to SV40 Tumor-Associated Specific Antigen

The H-2 gene complex controls the ability of mice to generate cytotoxic T cells to the SV40 tumor-associated specific antigen (TASA). Mice of six H-2 haplotypes (H-2b, d, f, k, q, and s) were challenged in vivo with syngeneic simian virus 40 (SV40)-transformed cells. By testing splenic lymphocytes in a 51Cr cytotoxic test, only H-2b mice were able to generate cytotoxic T cells specific for syngeneic SV40-transformed target cells. In contrast, immune lymphocytes from both H-2b and H-2k mice assayed after secondary in vitro restimulation lysed SV40-transformed target cells of appropriate H-2 genotype. Popliteal lymph node cells from H-2b, k, and d mice, immunized by footpad injection of SV40 and then incubated for 14 days in vitro before assay, are cytotoxic for syngeneic SV40-transformed cells. With this immunization protocol, H-2b mice respond to SV40 TASA in association with both the H-2 K and D locus-coded molecules, whereas H-2k mice respond to SV40 TASA in association with the H-2 K molecule only and H-2d mice respond to SV40 TASA in association with the H-2 D gene product. SV40 TASA-immune lymphocytes from various F1 (responder × nonresponder) mice were also unable to lyse syngeneic H-2Kd or H-2Dk SV40-transformed target cells. Inhibition of the response to SV40 TASA in association with H-2Dd is found when lymphocytes from SV40 TASA-immune F1 hybrid (H-2b × H-2d) or H-2 congenic recombinant (H-2KbDd) mice are analyzed. A dominant suppression or recessive helper mechanism is hypothesized to account for these results.