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.
Lanier
L L
LL
Department of Human Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304.
Gumperz
J E
JE
Parham
P
P
Melero
I
I
López-Botet
M
M
Phillips
J H
JH
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology*; D015236:HLA-C Antigens / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D011971:Receptors, Immunologic / Q000737:chemistry / Q000276:immunology*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D014162:Transfection
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1