Mechanism of interaction of pH 3.0 treated tumor cells expressing lower levels of class I MHC antigens, with IL-2 activated NK cells.
Effect of lowering the levels of class I MHC antigens, on the ability of three murine (YAC, P815, SP2O) and three human (Molt4, Raji, HR7) tumor cell lines, to compete in cold target inhibition assays, was studied. Specific reduction in class I MHC levels (range 60-76%) was induced by brief exposure to citrate buffer (pH 3.0). Susceptibility of the acid pH treated tumor cells to lysis by IL-2 activated NK cells, was found to be significantly increased in all cases with the exception of YAC cells. Reduction in class I MHC antigen expression by acid pH treatment, had no significant effect on competing ability of the tumor cells. In contrast, tumor cells on which MHC class I antigens were upregulated by interferon treatment, had significantly lower ability to compete. These results suggest that the mechanisms of altered interactions between MHC I up or down regulated target cells may be different. A model compatible with increased NK susceptibility along with an unaltered ability to compete for acid pH treated tumor cells, has been proposed.
Haridas
V
V
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Saxena
R K
RK
D000818:Animals; D001667:Binding, Competitive; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured / Q000502:physiology
D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D007371:Interferon-gamma