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) t umor cell lines, to compete in cold target inhibition assays, was stud ied. Specific reduction in class I MHC levels (range 60-76%) was induc ed 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 tre atment, had no significant effect on competing ability of the tumor ce lls. In contrast, tumor cells on which MHC class I antigens were upreg ulated by interferon treatment, had significantly lower ability to com pete. These results suggest that the mechanisms of altered interaction s between MHC I up or down regulated target cells may be different. A model compatible with increased NK susceptibility along with an unalte red ability to compete for acid pH treated tumor cells, has been propo sed. (C) 1997 Elsevier Science B.V.