The NKB1 and HP-3E4 NK cells receptors are structurally distinct glycoproteins and independently recognize polymorphic HLA-B and HLA-C molecules.

NK cells lyse hematopoietic cells that lack expression of MHC class I molecules on the cell surface. Transfection of certain MHC class I negative cell lines with MHC class I genes renders these cells resistant to NK cell-mediated cytotoxicity. Recently, we described an NK cell receptor, NKB1, that inhibits NK cells from killing target cells expressing Bw4-reactive HLA-B molecules (-B*2705, -B*5101, -B*5801). In this study, we have demonstrated that another structurally distinct NK cell membrane glycoprotein, HP-3E4, is involved in the recognition of certain polymorphic HLA-C molecules (-Cw*0401 and -Cw*1503). NK cell clones co-expressing both the NKB1 and HP-3E4 receptors fail to lyse targets expressing HLA-Cw*0401 and -B*5801, but are able to kill the transfectants in the presence of mAbs against both receptors. These studies demonstrate that a single NK cell clone may possess multiple structurally distinct receptors for different polymorphic HLA class I molecules that function independently.