IMMUNOLOGICAL AND NONIMMUNOLOGICAL INFLUENCE OF H-2KB GENE TRANSFECTION ON THE METASTATIC ABILITY OF B16 MELANOMA-CELLS

The H-2b-negative B78H1 clone (derived from B16 melanoma) was transfected with the H-2K(b) gene; 4 cell clones expressing membrane H-2K(b) antigens and 2 control clones (transfected with pSV2neo alone) were used for studies of metastatic ability, immunogenicity, NK sensitivity and homotypic adhesion. The experimental metastatic capacity of H-2K(b) transfectants in syngeneic mice was greatly diminished in comparison with control and parent cells. Both immune-mediated and intrinsic properties of transfectants correlated with their lower metastatic ability. A cell-mediated cytotoxic response was induced by repeated in vivo immunizations of syngeneic mice followed by in vitro restimulation of effectors when transfectants (but not controls) were used as immunizers and as targets. Moreover, homotypic adhesion of H-2K(b) transfectants was significantly lower than that of controls. Sensitivity to NK cells of transfectants was not decreased in comparison to H-2-negative controls. It is known that in vitro treatment with IFN-gamma of H-2-positive B16 melanoma cells induces a simultaneous increase in H-2 expression and in experimental metastasis; treatment of H-2K(b) transfectants with IFN-gamma induced a higher K(b) expression, but no increase in metastatic ability, thus suggesting that the IFN-sensitive component that mediates enhancement of metastasis is not H-2K(b).