THE ROLE OF MHC CLASS-I EXPRESSION IN RAT NK CELL-MEDIATED LYSIS OF SYNGENEIC TUMOR-CELLS AND VIRUS-INFECTED CELLS

In this study the role of MHC class I antigen expression in rat natura l killer (NK) cell-mediated lysis was investigated. Various rat tumor cell lines and two Adenovirus (Ad)-transformed rat cell lines were tes ted for their expression levels of total MWC class I and two MHC class I alleles, RT1.A and RT1.C, by flow cytometry. Their susceptibility t o NK cell-mediated lysis in relation to MHC class I expression was det ermined by Cr-51 release assays. IFN-gamma is know to increase the exp ression of MHC class I. Therefore target cell with and without prior I FN-gamma treatment were examined for MHC class I expression and its ef fect on NK lysis. An significant inverse exponential relationship was found. To investigate the effect of virus infection on MHC class I exp ression and target cell lysis by NK cells, rat embryonal fibroblasts ( REF) were infected with cytomegalovirus (CMV) and used as target cells for NK cell-mediated lysis. Results showed that these virus-infected cells were less susceptible to NK lysis than non-infected cells. Moreo ver, the non-infected cells expressed less MHC class I than the infect ed cells, indicating that also in this case, there was an inverse corr elation between MHC class I expression and susceptibility to lysis by NK cells. Subsequently, we showed that sorted subsets of predominantly CD8-positive and CD8-negative NK cells lysed a MHC class I-positive t umor cell line at the same level. This suggests that CD8 is not likely to participate as a receptor for MHC class I in NK cell-mediated lysi s in a syngeneic rat model.