Variation of expression of histocompatibility antigens on tumor cells: absence of H-2Kk-gene products from a gross-virus-induced leukemia in BALB.K

The antigenic profile of the K-GV tumor of BALB.K origin, induced by Gross virus and maintained in vitro and in vivo, was investigated by serological and immunochemical methods and techniques of cell-mediated immunity. The H-2Kk-gene products were absent by several criteria: (1) monoclonal antibody and conventional alloantisera directed against eh H-2Kk antigenic specificities were nonreactive by direct testing and by absorptions. (2) H-2Kk products could not be precipitated from glycoprotein or protein extracts of the radiolabeled K-GV tumor. (3) Cytotoxic effectors against H-2Kk produced by sensitization in vitro and in vivo failed to kill K-GV target cells. (4) The tumor could neither stimulate BALB.B congenic mice to produce cytotoxic effectors nor specific cytotoxic antibody against H-2Kk-gene products. In contrast, the H-2Dk antigen was readily detectable by all these criteria. These findings therefore describe a tumor which has selectively lost the H-2K-gene products. The K-GV tumor was able to generate Gross-virus specific CTL, but had greatly reduced susceptibility to lysis by Gross-virus specific CTL generated by H-2K expressing AKR (H-2k) tumors. These findings have important implications for the associative recognition of tumor antigens and the immune surveillance of virally induced tumors.