A NATURAL-KILLER-CELL RECEPTOR-SPECIFIC FOR A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULE

Target cell expression of major histocompatibility complex (MHC) class I molecules correlates with resistance to lysis by natural killer (NK) cells. Prior functional studies of the murine NK cell surface molecule, Ly-49, suggested its role in downregulating NK cell cytotoxicity by specifically interacting with target cell H-2D(d) molecules. In support of this hypothesis, we now demonstrate a physical interaction between H-2D(d) and Ly-49 in both qualitative and quantitative cell-cell binding assays employing a stable transfected Chinese hamster ovary (CHO) cell line expressing Ly-49 and MHC class I transfected target cells. Binding occurred only when CHO cells expressed Ly-49 at high levels and targets expressed H-2D(d) by transfection. Monoclonal antibody blocking experiments confirmed this interaction. These studies indicate that the specificity of natural killing is influenced by NK cell receptors that engage target cell MHC class I molecules.