Membrane Cofactor Protein (CD46)

Membrane cofactor protein (MCP), also known as CD46 (cluster of differentiation 46), is a complement regulatory transmembrane glycoprotein that plays a crucial role in suppressing autoimmune responses and protecting host cells from complement-mediated damage. The MCP protein encoded by the CD46 gene has four isoforms, each of which contains four complement control protein (CCP) modules which contains the C3b and C4b binding sites and is responsible for cofactor activity. However, the four CCP modules differ in glycosylation and core proteins that extend from the cell membrane. MCP is expressed on all nucleated human cells such as T cells, B cells, natural killer cells, monocytes, neutrophils, platelets, endothelial cells, epithelial cells, fibroblasts, placenta, and sperm.

MCP acts as a cofactor for complement factor I, responsible for cleavage of C3b and C4b on host tissue, and protecting host cells from complement-mediated attack. It may also act as a costimulatory factor for T-cells, inducing the differentiation of CD4+ into T-regulatory 1 cells which suppress immune responses by secreting interleukin-10. In addition, MCP may be associated with the fusion of the spermatozoa with the oocyte during fertilization. Deficiencies of MCP are associated with atypical hemolytic uremic syndrome (aHUS) and many autoimmune diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE).

Fig. 1 Structure of CD46.¹

Reference

1. Delpeut, Sebastien, Ryan S. Noyce, and Christopher D. Richardson. "The tumor-associated marker, PVRL4 (nectin-4), is the epithelial receptor for morbilliviruses." Viruses 6.6 (2014): 2268-2286.