LAIR-1, a Novel Inhibitory Receptor Expressed on Human Mononuclear Leukocytes

Abstract

In the present study, we describe a novel inhibitory receptor, leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), that is constitutively expressed on the majority of human peripheral blood mononuclear leukocytes. LAIR-1 is a 32 kDa transmembrane glycoprotein with a single immunoglobulin-like domain and a cytoplasmic tail containing two immune receptor tyrosine-based inhibitory motifs. LAIR-1 recruits SHP-1 and SHP-2 phosphatases upon activation, and cross-linking of the LAIR-1 antigen on natural killer (NK) cells results in strong inhibition of NK cell–mediated cytotoxicity. Although it is structurally related to human killer cell inhibitory receptors, LAIR-1 does not appear to recognize human leukocyte antigen (HLA) class I molecules and thus represents a novel HLA class I–independent mechanism of NK cell regulation.