Selective depletion of human natural killer cells on monolayers of target cells

The specificity of human natural killer (NK) cells recently has been evaluated by examining direct cytotoxic reactions against a variety of target cells and by cold target inhibition assays. Although these studies have provided evidence for the multiplicity of NK antigens, they did not indicate whether NK cells were heterogeneous, with subpopulations recognizing different specificities. We have examined this issue by using a tumor cell-monolayer adsorption technique that allowed the removal of NK-reactive cells by adsorption to monolayers of various NK-sensitive target cells. After depletion of cells capable of binding to a particular monolayer, the remaining cells were tested for cytotoxicity against a panel of 5 target cells. With several donors, the monolayers were effective in depleting most or all reactivity against the same target cell but only removed a portion of reactivity against some other target cells. The patterns of reactivity after adsorption, although varying among the donors, were consistent upon repeat testing of the same donor. To account for the reactivities of the various donors that remained after adsorption, it was necessary to postulate at least 7 antigenic specificities. These results indicate that human NK cells may be heterogeneous, with each subpopulation recognizing different antigenic specificities on target cells.