Genetic control of the induction of cytolytic T lymphocyte responses to AKR/Gross viral leukemias. I. H-2-encoded dominant gene control.

Previously, a system was devised whereby H-2-restricted cytotoxic T lymphocytes could be raised that were specific for tumors induced by endogenous AKR/Gross murine leukemia virus and that displayed the Gross cell surface antigen (GCSA). The generation of such anti-AKR/Gross virus CTL required in vivo priming with allogeneic (H-2 and/or non-H-2 incompatible) GCSA+ tumor cells, followed by in vitro restimulation with H-2-compatible GCSA+ tumor cells. The prototype responder strain of mice was C57BL/6, which is of the H-2b type and which has a low incidence of spontaneous virus-induced leukemia ("low leukemic"). Present experimentation indicates that there is H-2-encoded control of the ability to mount an anti-AKR/Gross virus CTL response. In addition to C57BL/6, all other H-2b strains tested, including C57BL/10, C57L, and 129, were responders. In contrast, H-2k strains of both "high leukemic" (AKR) and "low leukemic" (AKR.Fv-1b and CBA) phenotype appeared to be low- or nonresponders with respect to their ability to generate H-2k-restricted anti-AKR/Gross virus CTL after appropriate stimulation. Furthermore, B6.H-2k congenic mice were also poorly responsive, suggesting that H-2b and H-2k were responder and nonresponder haplotypes, respectively. The finding that (responder X nonresponder)F1, i.e., (B6 X CBA)F1 mice mounted CTL responses to H-2b, but not H-2k, GCSA+ tumors, was consistent with this interpretation and suggested the presence of H-2-encoded dominant immune response genes. The tumors of AKR background that were efficient in the in vivo priming of C57BL/6 mice were relatively inefficient in priming (B6 X CBA)F1 mice for a subsequent in vitro H-2b-restricted anti-AKR/Gross virus CTL response. Because of the similarities in background minor H genes of the AKR and CBA strains, this latter observation was in keeping with the requirement for in vivo stimulation with tumor cell alloantigens in addition to the virus-associated target antigens.