[Reduced expression of class I MHC antigens in NIH3T3 cells transformed with activated ras oncogenes]

For CTL-mediated lysis of tumor cells the existence of class I molecules is required, in addition to tumor specific antigens, on the cell surface. Therefore, it is likely that tumor cells with altered class I antigen expression might escape from immune surveillance by T-cells. There have been many reports that virally-or chemically-induced murine and human tumor cells and/or tissues expressed reduced number of cell surface class I molecules. However, it is unknown how the regulatory pathway of class I antigen expression and the intracellular oncogenic cascade are interrelated. In this report, class I antigen expressions in NIH3T3 cells transformed with activated ras genes are analyzed. Transformed cells were tumorigenic in allogeneic immunocompetent mice and less sensitive to allogeneic killer T-cells than untransformed NIH3T3. The levels of cell surface expression of H-2K and H-2D region products analyzed using a monoclonal antibodies and a flow-cytometer showed marked reduction of antigen expression in the transformants. Scatchard analysis of the binding of monoclonal antibodies to cell-surface class I molecules indicated that the affinity of the reaction was unchanged after transformation of NIH3T3 cells with activated N-ras oncogene, thus confirmed that the reduced expression observed by flow-cytometric analysis was due to decreased number of the antigen in the transformants. Northern hybridization analyses of H-2 class I and B2-microglobulin transcripts showed that the amounts of both class I and B2-microglobulin mRNAs paralleled with the levels of cell surface expression of the antigen.(ABSTRACT TRUNCATED AT 250 WORDS)