The Journal of Immunology, Vol 154, Issue 7 3320-3327, Copyright © 1995 by American Association of Immunologists

ARTICLES

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

LL Lanier, JE Gumperz, P Parham, I Melero, M Lopez-Botet and JH Phillips
Department of Human Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304.

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.

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