Resistance to cellular immune response in AKR leukemias

Abstract

Spontaneous AKR leukemias express murine leukemia virus (MuLV) gag and env gene-encoded structural proteins on their cell surface. Cytotoxic T lymphocytes (CTL) induced in AKR mice by syngeneic leukemia 369 which expressed high amounts of H-2 antigens recognized viral gag polyproteins in association with H-2K antigens as target antigens. H-2K-negative leukemias were resistant to lysis by AKR/Gross MuLV-specific CTL and did not induce a cellular immune response. However, they became susceptible after stimulation with interferon. H-2K-positive leukemias induced CTL which were cytotoxic for 369 cells. However, the majority of H-2K-positive leukemias was not lysed by CTL induced by autologous immunization. These leukemias were also resistant to lysis by anti-369 CTL, but could restimulate AKR/Gross-specific CTL in vitro, and were susceptible to lysis by H-2Kk-restricted CTL against AKR minor histocompatibility antigens. Thus, there could be specific defects of the H-2Kk antigens of these tumors. However, there were also qualitative and quantitative differences in antigenic determinants of the gag target antigens in these leukemias. Therefore, in addition to quantitative reduction of the H-2K restriction elements, qualitative alterations of H-2 antigens or of the viral target antigens may impair T cell cytotoxicity and thus influence leukemogenesis of AKR spontaneous leukemia.