CD200

Fig1. CD200-CD200R axis is considered to be a pair of checkpoint molecules that regulate tumor-specific immune responses. (Jin-Qing Liu, 2020)

What is CD200 protein?

CD200 (CD200 molecule) gene is a protein coding gene which situated on the long arm of chromosome 3 at locus 3q13. This gene encodes a type I membrane glycoprotein containing two extracellular immunoglobulin domains, a transmembrane and a cytoplasmic domain. This gene is expressed by various cell types, including B cells, a subset of T cells, thymocytes, endothelial cells, and neurons. The encoded protein plays an important role in immunosuppression and regulation of anti-tumor activity. The CD200 protein is consisted of 278 amino acids and its molecular mass is approximately 31.3 kDa.

What is the function of CD200 protein?

CD200 is an immune checkpoint molecule that is mainly expressed on the surface of antigen presenting cells (APC). It interacts with the receptor CD200R to negatively regulate the immune response and maintain the immune balance. The main functions of CD200 protein include: 1) inhibiting T cell proliferation and cytokine production, reducing excessive immune response; 2) Regulate macrophage differentiation and function, and affect inflammatory response; 3) Inhibit the killing activity of NK cells and CD8+T cells to prevent the occurrence of autoimmune diseases and allergic reactions.

CD200 Related Signaling Pathway

CD200 protein is an immune checkpoint molecule that exerts negative immunomodulatory effects by binding to the receptor CD200R and inhibiting the activation and proliferation of T cells. In addition, CD200 protein is also involved in some other signaling pathways, such as Notch signaling pathway, NF-κB signaling pathway, etc., affecting cell differentiation, apoptosis and other biological processes.

Fig2. Multiple mechanisms underly the pro-tumorigenic role of CD200. (Anqi Shao, 2023)

CD200 Related Diseases

CD200 is abnormally expressed in a variety of tumors, including malignant melanoma, breast cancer, lung cancer, and pancreatic cancer. CD200 is upregulated in some autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. CD200 plays a role in the infection of certain pathogens, such as hepatitis C. CD200 has also been linked to a number of other diseases, such as multiple sclerosis, stroke and so on.

Bioapplications of CD200

CD200 is associated with a variety of diseases, and antibodies or small molecule inhibitors targeting CD200 protein can be used in the study of treatment of related diseases. By regulating the expression level of CD200 protein, the immune tolerance of grafts can be affected, thus reducing the occurrence of transplantation rejection.

Case Study 1: Karrie K Wong, 2016

The researchers have previously reported the existence of a soluble form of CD200 (sCD200) in human plasma, and found sCD200 to be elevated in the plasma of Chronic Lymphocytic Leukemia (CLL) patients. CLL cells release CD200 at a constitutive level, which could be attenuated partially by ADAM28 silencing. In this study, they further explored mechanisms of CD200 shedding beyond that of ADAM28, and performed biochemical analysis of sCD200 using materials derived from purified CLL cells and Hek293 cells stably transfected with CD200, and antibodies generated specifically against either the extracellular or cytoplasmic regions of CD200. CD200 shedding was enhanced by PMA stimulation, and the loss of cell surface CD200 could be monitored as a reduction in CD200 cell surface expression by flow cytometry, in parallel with an increase in the detection of sCD200 in the supernatant. Western blot analyses and functional studies using CD200R1 expressing Hek293 cells showed that the shed CD200 detected in CLL and Hek293-hCD200 supernatants lacked the cytoplasmic domain of CD200 but retained the functional extracellular domain required for binding to, and phosphorylation of, CD200R.

Fig1. PMA-induced CD200 shedding is reflected as a loss of CD200 expression from the surface of CLL cells.

Fig2. Characterization of rabbit anti-CD200 c-tail serum.

Case Study 2: Haitao Qian, 2024

Following hypoxic-ischemic brain damage (HIBD), there is a decline in cognitive function; however, there are no effective treatment strategies for this condition in neonates. This study aimed to evaluate the role of the cluster of differentiation 200 (CD200)/CD200R1 axis in cognitive function following HIBD using an established model of HIBD in postnatal day 7 rats. Western blotting analysis was conducted to evaluate the protein expression levels of CD200, CD200R1, proteins associated with the PI3K/Akt-NF-κB pathway, and inflammatory factors such as TNF-α, IL-1β, and IL-6 in the hippocampus. HIBDleads to a decrease in the expression of CD200 and CD200R1 proteins in the neonatal rat hippocampus, while simultaneously increasing the expression of TNF-α, IL-6, and IL-1β proteins, ultimately resulting in cognitive impairment. The administration of CD200Fc, a fusion protein of CD200, was found to enhance the expression of p-PI3K and p-Akt, but reduce the expression of p-NF-κB. Additionally, CD200Fc inhibited M1 polarization of microglia, reduced neuroinflammation, improved hippocampal neurogenesis, and mitigated cognitive impairment caused by HIBD in neonatal rats. In contrast, blocking the interaction between CD200 and CD200R1 with the anti-CD200R1 antibody (CD200R1 Ab) exerted the opposite effect.

Fig3. Immunofluorescent staining showing that CD200 was colocalized with neurons.

Fig4. CD200Fc reduced the expression levels of TNF-α, IL-6 and IL-1β by suppressing the NF-κB-mediated M1 polarization of microglia via the PI3K/Akt signaling pathway.

CD200 has several biochemical functions, for example, cell adhesion molecule binding,protein binding,protein homodimerization activity. Some of the functions are cooperated with other proteins, some of the functions could acted by CD200 itself. We selected most functions CD200 had, and list some proteins which have the same functions with CD200. You can find most of the proteins on our site.

CD200 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CD200 here. Most of them are supplied by our site. Hope this information will be useful for your research of CD200.

CD200R1;HUS1