Molecular Identification of a Novel Family of Human Ig Superfamily Members That Possess Immunoreceptor Tyrosine-based Inhibition Motifs and Homology to the Mouse Gp49B1 Inhibitory Receptor

The co-cross-linking of gp49B1, a member of the Ig superfamily containing immunoreceptor tyrosine-based inhibition motifs, with the high affinity Fc receptor for IgE on mouse bone marrow culture-derived mast cells inhibits IgE-dependent exocytosis and lipid mediator generation. We now describe the cloning of human cDNAs homologous to the mouse gp49 family. A human monocyte cDNA library was probed with the mouse gp49A cDNA, which is 97% identical with mouse gp49B1, to obtain a homologous partial cDNA that was then used to identify and clone full-length cDNAs from monocyte and human lung cDNA libraries. The 1.6-kbp cDNA, HM18, predicts a 49-kDa type 1 integral membrane protein that, like mouse gp49B1, contains two extracellular C2 type Ig superfamily domains and two consensus immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic domain. ALIGN analysis of the amino acid sequence of the extracellular domains showed that HM18 belongs to a family that includes mouse gp49, the bovine Fc receptor for IgG2, the human myeloid Fc receptor for IgA, and the human NK cell inhibitory receptors. The gene encoding HM18, in common with the genes for the human Fc receptor for IgA and the human NK cell inhibitory receptors, was localized to chromosome 19q13.4. Two other closely related cDNAs, each with four C2 Ig superfamily domains, were characterized. Transcripts for these novel Ig superfamily members were identified in peripheral blood monocytes, the THP-1 monocytic cell line, human lung, human lung mast cells, and NK cells. The data suggest that HM18 is a novel mononuclear cell inhibitory receptor homologous to mouse gp49B1.