29744 bp

The CD200 molecule is a single-pass type I membrane protein spanning the membrane once, with its N-terminus on the extracellular side of the membrane and subsequent processing results in removal of its signal sequence. Variant 1 produces a protein that is 269 amino acids in length, variant 2 yields a protein that is 294 amino acids, and variant 3 has yet to be experimentally validated for its product. CD200 is a highly conserved member of the immunoglobulin superfamily containing both an Ig-like C2-type (immunoglobulin-like) domain as well as Ig-like V-type (immunoglobulin-like) domain.

CD200 is commonly expressed on cells originating from the hematopoietic cells, specifically those of the myeloid lineage such as macrophages, dendritic cells, neutrophils, mast cells, and eosinophils, yet it can also be expressed on B cells, activated T cells, endothelial neuronal cells and cells of the reproductive organs (ovaries and placental trophoblasts). This molecule exerts its effect by binding to its cognate receptor CD200R (also on chromosome 3 and containing two Ig-like domains) which is expressed on cells specifically derived from the myeloid lineage and certain populations of T cells. This interaction can only occur when the cell carrying the receptor and the cell expressing CD200 are in close contact to one another. Unlike the CD200 molecule itself, the CD200R has 67 amino acids in its cytoplasmic domain compared to 19 for CD200, and it contains tyrosine residues that can be phosphorylated to carry on further signal transduction. A recent review has further summarized the tissue distribution of CD200 and its receptor in rat, mouse and human samples.

Single-pass type I plasma membrane protein or plasma membrane associated protein.

The function of CD200 was orginally identified using mice lacking the CD200 gene where the mice developed an earlier onset of disease in experimental models of both autoimmune encephalomyelitis (EAE), collagen-induced arthritis (CIA), and autoimmune alopecia. The mice have increased numbers of macrophages in the spleen and after immunological stimulation, these macrophages demonstate a more active phenoype in vivo. These studies demonstrate the importance of CD200 in maintaining self-tolerance and further studies have demonstrated that CD200 acts as an important molecule in controlling autoimmunity, inflammation and adaptive immune responses implicating it as a key immunosuppressive molecule. The CD200-CD200R interaction exerts its inhibitory signal to myeloid cells that suppresses INF (Interferon)-gamma-induced proliferation, activation and secretion of nitrous oxide (NO), IL5, IL13 and IL6. Interestingly, a few phylogenetically distinct viruses including poxviruses and KSHV, the agent that causes Kaposi sarcoma and other human cancers, have been shown to attenuate the host antiviral immune response by expressing a viral CD200 homolog.

None noted.

Restricted CD200R isoform expression at the feto-maternal interface suggests CD200-CD200R interactions may serve important function(s) determining the successful outcome of pregnancy.