THE SUSCEPTIBILITY TO NATURAL-KILLER CELL-MEDIATED LYSIS OF HLA CLASSI-POSITIVE MELANOMAS REFLECTS THE EXPRESSION OF INSUFFICIENT AMOUNTS OF DIFFERENT HLA CLASS-I ALLELES

NK cells selectively lyse tumor cells which do not express one or more MHC class lalleles. The ability to discriminate between self normal o r tumor cells is due to the expression of MHC class I-specific killer inhibitory receptors (KIR). In the present study we analyzed melanoma cell lines which were highly susceptible to NK cell-mediated lysis in spite of the expression of a complete set of HLA class I alleles. Quan titative analysis of the HLA class I expression using allele-specific monoclonal antibodies (mAb) revealed a down-regulation of all HLA clas s I molecules. Treatment of melanoma cells with IFN-gamma resulted in up-regulation of all HLA class I alleles that was paralleled by the ac quisition of resistance to lysis. That resistance to lysis reflected t he up-regulation of HLA class I molecules was revealed by the finding that mAb-mediated masking of either KIR or their HLA class I ligands c ompletely restored the melanoma cell lysis. These results were obtaine d by the use of selected NK cell clones derived either from allogeneic or autologous donors. In addition, similar results were obtained usin g in vitro expanded autologous NK cell populations. Our data indicate that NK cells can lyse not only melanoma cells which have lost the exp ression of one or more HLA class I alleles but also cells expressing a decreased amount of class I molecules.