MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-INDEPENDENT KILLING OF XENOGENIC TARGETS BY RAT ALLOSPECIFIC NATURAL-KILLER-CELLS

Major histocompatibility complex class I molecules can inhibit mouse a s well as human natural killer (NK) cell cytotoxicity, In contrast, an tigens encoded in the RT1.C region of the rat MHC gene complex have be en suggested to trigger, rather than inhibit, rat Nh cells. In an atte mpt to analyze rat NR cell specificity, with respect to the cross-spec ies difference that may exist in NK cell-mediated cytotoxicity, we inv estigated the ability of interleukin 2-activated, allospecific rat Nh cells to recognize MHC class I-positive and -deficient target cells of mouse and human origins. Recognition of xenogeneic target cells by ra t allospecific NK cells was found to be MHC class I independent; targe t cell MHC class I was not required for billing, and expression of dif ferent sets of mouse and human MHC class I molecules did not influence the cytotoxic response. These results indicate that rat NK cells can recognize xenogeneic nontransformed cells by mechanisms not related to target cell MHC class I expression, and that mouse and human MRC clas s I molecules, at least among those tested in this study, are unable t o confer inhibition of rat NR cells.