A NOVEL IMMUNOGLOBULIN SUPERFAMILY RECEPTOR FOR CELLULAR AND VIRAL MHC CLASS-I MOLECULES

The human cytomegalovirus UL18 gene product is a homolog of cellular m ajor histocompatibility (MHC) class I antigens. UL18 has been proposed to protect virus-infected cells against natural killer (NK) cell cyto toxicity by engaging NK cell killer inhibitory receptors (KIR) for MHC class I. UL18 binds to a novel immunoglobulin superfamily glycoprotei n, designated Leukocyte Immunoglobulin-like Receptor (LIR-1). This pro tein is distinct from, but related to, known KIRs and binds cellular M HC class I antigens. The cytoplasmic domain of LIR-1 contains four put ative immunoreceptor tyrosine-based inhibitory motifs. Upon tyrosine p hosphorylation, LIR-1 associates with the tyrosine phosphatase SHP-1. In contrast to KIRs, LIR-1 is expressed predominantly on monocytic and B lymphoid cell types, suggesting a distinct biological function.