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Gene Review

Cd200  -  CD200 antigen

Mus musculus

Synonyms: MRC OX-2, MRC OX-2 antigen, Mox2, OX-2 membrane glycoprotein, OX2
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Disease relevance of Cd200

  • Onset and severity of uveitogenic peptide (1-20) of interphotoreceptor retinoid-binding protein-induced experimental autoimmune uveoretinitis is accelerated in CD200(-/-) mice and although tissue destruction appears no greater than seen in CD200(+/+) mice, there is continued increased ganglion and photoreceptor cell apoptosis [1].
  • Despite earlier onset of experimental autoimmune uveitis in sham-tolerized, CD200-deficient mice, disease incidence and subsequent severity were actually reduced compared with those in wild-type mice [2].
  • Halting disease progression and tolerance in CD200(-/-) mice correlated with a marked increase in Th2-associated cytokine production by Ag-challenged splenocytes [2].
  • Because manipulation of the CD200-CD200R interaction affects the outcome of rodent disease models, targeting of this pathway may have therapeutic utility [3].
  • Double-immunofluorescence staining of cerebellar interneurone cultures with MRC OX-2 antibody and tetanus toxin showed that all tetanus-positive cells (neurones) were MRC OX-2-positive [4].

High impact information on Cd200

  • Down-regulation of the macrophage lineage through interaction with OX2 (CD200) [5].
  • Upon facial nerve transection, damaged CD200-deficient neurons elicited an accelerated microglial response [5].
  • Putting the brakes on innate immunity: a regulatory role for CD200 [6]?
  • In all, we provide direct evidence that the CD200-CD200R interaction controls monocyte/macrophage function in both murine and human systems, further supporting the potential clinical application of CD200R agonists for the treatment of chronic inflammatory diseases [7].
  • Enhanced tolerance to autoimmune uveitis in CD200-deficient mice correlates with a pronounced Th2 switch in response to antigen challenge [2].

Biological context of Cd200

  • In CD200(-/-) mice the release of suppression of tonic macrophage activation, supported by increased NOS2 expression in the CD200(-/-) steady state accelerates disease onset but without any demonstration of increased target organ/tissue destruction [1].
  • Thus, mice lacking CD200 (CD200(-/-)) show increased susceptibility to and accelerated onset of tissue-specific autoimmunity [1].
  • Collectively, these results suggest that the expression of CD200 in follicular epithelium attenuates inflammatory reactions and may play a role in maintaining immune tolerance to HF-associated autoantigens [8].
  • We now report that freshly isolated cells of the murine epidermis contain a subpopulation of major histocompatibility complex (MHC) class II-negative, CD3-negative keratinocytes that are CD200-positive [8].
  • Blocking MD-1 gene expression inhibits surface expression of CD80 and CD86, but not of OX2 [9].

Anatomical context of Cd200


Associations of Cd200 with chemical compounds


Regulatory relationships of Cd200


Other interactions of Cd200

  • When syngeneic skin grafts were exchanged between gender-matched wild-type (WT) and CD200-deficient C57BL/6 mice, significant perifollicular and intrafollicular inflammation was observed, eventually leading to the destruction of virtually all HF (alopecia) without significant loss of the CD200-negative grafts [8].
  • Engagement of CD200R by CD200 inhibits activation of myeloid cells [13].
  • Increased expression of OX2 on dendritic cells (DC) in vivo following preimmunization via the portal vein is also associated with elevated expression of MD-1 [9].
  • The immunoadhesin (OX2:Fc) comprising the extracellular domain of murine OX2 linked to IgG2aFc, inhibits production of IL-2 and IFN-gamma by activated T cells and increases allograft and xenograft survival in vivo [9].
  • BACKGROUND: CD200 is a transmembrane protein delivering immunoregulatory signals after engagement of CD200R [14].

Analytical, diagnostic and therapeutic context of Cd200

  • The CD200-COMP gave strong signals in protein microarrays, suggesting that such reagents may be valuable in high throughput detection of weak interactions [10].
  • The epitope for the MRC OX2 mAb and a site for ligand binding were mapped to domain 1 by site-directed mutagenesis [15].
  • RESULTS: Only mAbs defining epitopes in the N-terminal domain could augment MLC reactivity (or block immunosuppression by soluble CD200Fc), whereas mAbs targeting C-domain epitopes, although reactive in ELISA or FACS (targeting cell surface CD200), were inactive in MLCs [16].
  • CD200 immunoadhesin suppresses collagen-induced arthritis in mice [17].
  • In vitro studies with an OX2:Fc immunoadhesion had suggested that immunosuppression induced by this soluble form of the OX2 molecule was dependent primarily upon an early (OX2-dependent) signal [18].


  1. Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis. Broderick, C., Hoek, R.M., Forrester, J.V., Liversidge, J., Sedgwick, J.D., Dick, A.D. Am. J. Pathol. (2002) [Pubmed]
  2. Enhanced tolerance to autoimmune uveitis in CD200-deficient mice correlates with a pronounced Th2 switch in response to antigen challenge. Taylor, N., McConachie, K., McConnachie, K., Calder, C., Dawson, R., Dick, A., Sedgwick, J.D., Liversidge, J. J. Immunol. (2005) [Pubmed]
  3. Characterization of the CD200 receptor family in mice and humans and their interactions with CD200. Wright, G.J., Cherwinski, H., Foster-Cuevas, M., Brooke, G., Puklavec, M.J., Bigler, M., Song, Y., Jenmalm, M., Gorman, D., McClanahan, T., Liu, M.R., Brown, M.H., Sedgwick, J.D., Phillips, J.H., Barclay, A.N. J. Immunol. (2003) [Pubmed]
  4. Localisation of the MRC OX-2 glycoprotein on the surfaces of neurones. Webb, M., Barclay, A.N. J. Neurochem. (1984) [Pubmed]
  5. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Hoek, R.M., Ruuls, S.R., Murphy, C.A., Wright, G.J., Goddard, R., Zurawski, S.M., Blom, B., Homola, M.E., Streit, W.J., Brown, M.H., Barclay, A.N., Sedgwick, J.D. Science (2000) [Pubmed]
  6. Putting the brakes on innate immunity: a regulatory role for CD200? Nathan, C., Muller, W.A. Nat. Immunol. (2001) [Pubmed]
  7. Regulation of myeloid cell function through the CD200 receptor. Jenmalm, M.C., Cherwinski, H., Bowman, E.P., Phillips, J.H., Sedgwick, J.D. J. Immunol. (2006) [Pubmed]
  8. Expression of CD200 on epithelial cells of the murine hair follicle: a role in tissue-specific immune tolerance? Rosenblum, M.D., Olasz, E.B., Yancey, K.B., Woodliff, J.E., Lazarova, Z., Gerber, K.A., Truitt, R.L. J. Invest. Dermatol. (2004) [Pubmed]
  9. Regulation of gene expression of murine MD-1 regulates subsequent T cell activation and cytokine production. Gorczynski, R.M., Chen, Z., Clark, D.A., Hu, J., Yu, G., Li, X., Tsang, W., Hadidi, S. J. Immunol. (2000) [Pubmed]
  10. Multivalent recombinant proteins for probing functions of leucocyte surface proteins such as the CD200 receptor. Voulgaraki, D., Mitnacht-Kraus, R., Letarte, M., Foster-Cuevas, M., Brown, M.H., Barclay, A.N. Immunology (2005) [Pubmed]
  11. Purification and chemical characterisation of membrane glycoproteins from rat thymocytes and brain, recognised by monoclonal antibody MRC OX 2. Barclay, A.N., Ward, H.A. Eur. J. Biochem. (1982) [Pubmed]
  12. Characterization of CD 200-receptor expression in the murine epidermis. Rosenblum, M.D., Woodliff, J.E., Madsen, N.A., McOlash, L.J., Keller, M.R., Truitt, R.L. J. Invest. Dermatol. (2005) [Pubmed]
  13. Molecular mechanisms of CD200 inhibition of mast cell activation. Zhang, S., Cherwinski, H., Sedgwick, J.D., Phillips, J.H. J. Immunol. (2004) [Pubmed]
  14. Augmented induction of CD4+CD25+ Treg using monoclonal antibodies to CD200R. Gorczynski, R.M., Lee, L., Boudakov, I. Transplantation (2005) [Pubmed]
  15. The leukocyte/neuron cell surface antigen OX2 binds to a ligand on macrophages. Preston, S., Wright, G.J., Starr, K., Barclay, A.N., Brown, M.H. Eur. J. Immunol. (1997) [Pubmed]
  16. Discrete monoclonal antibodies define functionally important epitopes in the CD200 molecule responsible for immunosuppression function. Chen, D.X., Gorczynski, R.M. Transplantation (2005) [Pubmed]
  17. CD200 immunoadhesin suppresses collagen-induced arthritis in mice. Gorczynski, R.M., Chen, Z., Yu, K., Hu, J. Clin. Immunol. (2001) [Pubmed]
  18. Evidence for persistent expression of OX2 as a necessary component of prolonged renal allograft survival following portal vein immunization. Gorczynski, R.M., Chen, Z., Kai, Y., Lei, J. Clin. Immunol. (2000) [Pubmed]
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