Resistance to cell-mediated cytotoxicity is correlated with reduction of H-2K gene products in AKR leukemia.

AKR leukemia cell lines differing in the amount of H-2K and H-2D antigens expressed on the cell surface were used to assess cell-mediated immune responses in syngeneic mice against Gross/AKR murine leukemia virus (MuLV)-induced tumors. Leukemic cells with reduced expression of H-2Kk antigens were inactive as inducers of Gross-MuLV/H-2k-specific cytotoxic T lymphocytes (CTL) and resistant to lysis by CTL raised against H-2Kk positive AKR leukemia cells. H-2Kk positive leukemias induced cytotoxic effectors, which upon restimulation in vitro, lysed the stimulating and other H-2Kk positive leukemia cells. In antibody inhibition experiments, T-cell-mediated cytotoxicity to these leukemias could only be inhibited by antisera and monoclonal antibodies specific for the H-2Kk antigens. Due to this specific role of H-2Kk antigens in T-cell cytotoxicity to Gross/AKR MuLV-induced tumors, reduced expression of H-2Kk antigens on spontaneous AKR leukemic cells could have important implications for surveillance of these neoplastic cells.