CD200

OX-2 membrane glycoprotein, also named CD200 (Cluster of Differentiation 200) is a human protein encoded by the CD200 gene. In humans, the CD200 gene is located on chromosome 3 in proximity to genes encoding the other B7 proteins CD80/CD86. In mice, the CD200 gene is located on chromosome 16.

The protein encoded by this gene is a type-1 membrane glycoprotein, which contains two IgSF immunoglobulin domains, transmembrane region and a 19 amino acid long cytoplasmatic domain. CD 200 belongs to the immunoglobulin superfamily, particularly belongs to the B7 receptor family.

CD200 is expressed on dendritic cells, activated B lymphocytes, activated T lymphocytes, thymocytes, endothelial cells, neurons and osteoblast precursors. Moreover, CD200 is expressed on various types of human cancer cells including hairy cell leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, melanoma, multiple myeloma, testicular cancer, renal carcinoma, colon carcinoma and glioblastoma multiforme.

In innate immunity, cellular CD200 expression is induced upon TLR and NLR activation.

At the transcriptional level, CD200 expression is regulated by C/EBP-β. It has been shown that CD200 expression is induced by IFN-γ and TNF-α in a NF-kappaB-, STAT1- and IRF-1-dependent manner.

Soluble CD200 (sCD200) is present in serum. It was shown that elevated levels of serum sCD200 are associated with adverse tumor prognosis in chronic lymphocytic leukemia, glioblastoma multiforme, ependymoma and medulloblastoma. Furthermore, sCD200 is associated with the expansion of myeloid-derived suppressor cells in patients with glioblastoma multiforme.

Truncated CD200 (CD200tr) is a truncated version of CD200 produced by alternative splicing mechanism. CD200tr lacks approximately 30 amino acids in the NH2-terminal sequence. It was shown that CD200tr acts as a competitive inhibitor to the full length CD200.

CD200 interacts with its receptor CD200R and leads to immunosuppressive signaling. CD200R is strongly expressed on macrophages, neutrophils and mast cells as well as on some subtypes of B lymphocytes and T lymphocytes. In the tumor microenvironment CD200R is expressed on tumor-associated myeloid cells, particularly in tumor-associate macrophages, myeloid-derived suppressor cells, tumor-associated dendritic cells and also in regulatory T lymphocytes.