J. Exp. Med.
© The Rockefeller University Press
0022-1007/96/12/2243/08 $2.00
Volume 184 December 1996 2243-2250

Killer Cell Inhibitory Receptor Recognition of Human Leukocyte Antigen (HLA) Class I Blocks Formation of a pp36/PLC- Signaling Complex in Human Natural Killer (NK) Cells

By Nicholas M. Valiante,^* Joseph H. Phillips, Lewis L. Lanier, and Peter Parham^*

From the ^* Departments of Structural Biology and Microbiology & Immunology, Stanford University Medical School, Stanford, California 94305; and the  Department of Human Immunology, DNAX Research Institute for Molecular and Cellular Biology, Palo Alto, California 94304

The killer cell inhibitory receptors (KIR) of human natural killer (NK) cells recognize human leukocyte antigen class I molecules and inhibit NK cell cytotoxicity through their interaction with protein tyrosine phosphatases (PTP). Here, we report that KIR recognition of class I ligands inhibits distal signaling events and ultimately NK cell cytotoxicity by blocking the association of an adaptor protein (pp36) with phospholipase C- in NK cells. In addition, we demonstrate that pp36 can serve as a substrate in vitro for the KIR-associated PTP, PTP-1C (also called SHP-1), and that recognition of class I partially disrupts tyrosine phosphorylation of NK cell proteins, providing evidence for KIR-induced phosphatase activity.

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