CD200R1

CD200R1 is the canonical inhibitory receptor for CD200, the founding member of a small gene cluster of CD200 receptor-like molecules (CD200R1, CD200R1L/CD200R2-CD200R5). CD200R1 is a 325-amino-acid type I transmembrane protein of the Ig superfamily, with an N-terminal V-set domain mediating CD200 binding and a cytoplasmic region containing three NPXY motifs that recruit Dok1/Dok2 and RasGAP to extinguish MAPK and PI3K signaling in myeloid cells. Expression is concentrated on macrophages, neutrophils, dendritic cells, mast cells, basophils and eosinophils, with inducible presence on T-cell subsets including regulatory T cells. CD200R1 engagement restrains lipopolysaccharide-driven inflammation, collagen-induced arthritis, experimental autoimmune encephalomyelitis, allergic asthma and corneal graft rejection, and maintains microglial quiescence during neurodegeneration. Polymorphisms in CD200R1 are associated with susceptibility to multiple sclerosis and HIV progression; tumor cells frequently overexpress CD200 to engage CD200R1 and suppress antitumor myeloid responses, spurring interest in disrupting the axis for cancer immunotherapy.