Kinetic analysis of the specificity of human natural cytotoxicity

Distribution-free analysis of kinetic data for cellular cytotoxicity reactions enables the precise determination of kinetic parameters for the lysis of target cells by individual lymphocyte preparations. This report presents results obtained when this method was used to quantitate the inhibition of human natural cytotoxicity by unlabelled (cold) target cells. In agreement with previous studies, we found that the natural cytotoxicity of a given target cell can be inhibited by heterologous as well as homologous unlabelled cells; however, the strongest inhibition was usually produced when the unlabelled inhibitor cells were homologous to the labelled target cells. The general pattern of inhibition observed for the target and inhibitor cells tested in these experiments was competitive, and when inhibitor cells were homologous to the labelled cells, the observed increase in Kappm agreed with theoretical predictions based on equations derived previously. These results support earlier reports of limited but not absolute antigenic specificity by subsets of human NK cells. Moreover, while Kappm values for cytotoxicity reactions are not simply related to antigen binding, quantitative analysis of the relative inhibition of cytotoxicity by heterologous versus homologous unlabelled cells provides useful estimates of the relative affinity of the effector cell subset(s) that kill a given target cell for various NK target cells.