Genetic control of CTL responses to AKR/Gross virus: effect of inheritance of Akv proviruses.

Our earlier observations suggested that the AKR/Gross leukemia virus-specific C57BL/6 cytolytic T lymphocyte (CTL) response was directed to Akv-1, but not Akv-3 or Akv-4, provirus-associated determinants. Based on these data, the present experiments were performed with various AKXL RI mouse strains of the responder H-2b haplotype which had inherited different combinations of the Akv-1, -3, and -4 proviruses, to determine whether these strains were able to mount specific antiviral CTL responses. In a comparison with control responder C57BL/6 mice, a clear pattern emerged. Akv-negative mice of the AKXL-29 strain were fully responsive, but five other AKXL strains which had inherited the Akv-1 provirus failed to mount significant antiviral CTL responses (less than or equal to 10% of control). In contrast, an Akv-1-negative but Akv-4-positive strain (AKXL-5) was partially responsive (approximately 24% of the C57BL/6 control). These results were consistent with a direct relationship between the Akv-1 provirus and the nominal antigens recognized by antiviral CTL, and with an inverse correlation between in vivo expression of viral antigens by normal cells and the ability to generate antiviral CTL. The possible mechanisms accounting for this unresponsiveness are discussed along with the utility of this system for investigating the interactions of retroviruses with the immune system.