T8282-12

Goat Anti-TREM-2 (Trem2, Triggering Receptor Expressed on Monocytes 2)

TREM-2 (Triggering Receptor Expressed by Myeloid cells) is an Ig superfamily cell surface receptor that activates a number of myeloid cell types. It is a member of a small gene family located on human chromosome 6p21 and mouse chromosome 17 in a region linked to the MHC. A single human TREM-2 gene has been described, however, two closely related orthologs were reported in mouse. The proteins differ by only three amino acids and were designated TREM-2a and TREM-2b. TREM-2 is type I transmembrane protein consisting of a single extracellular immunoglobulin (V-like) domain, a transmembrane domain with a positively charged lysine residue, and a short cytoplasmic tail. It associates with the signal adapter protein, DAP12, for signaling and function. DAP12 has a cytoplasmic ITAM that is phosphorylated upon ligand binding leading to the subsequent activation of cytoplasmic tyrosine kinases. TREM-2 is expressed by immature monocyte-derived dendritic cells (DC), and expression is down-regulated upon activation of DC by microbial products and costimulatory signals. Ligation of TREM-2 on immature DC with anti-TREM-2 antibodies results in partial DC activation and the up-regulation of CCR7 and some co-stimulatory molecules. A role for TREM-2 in the functioning of osteoclasts and microglia is suggested by the discovery that homozygous loss-of-function mutations in either TREM-2 or DAP12 result in Nasu-Hakola disease characterized by a combination of presenile demetia and bone cysts. In vitro studies indicate that the differentiation of myeloid precursors into osteoclasts is dramatically impaired in TREM-2 deficient individuals.