Complement receptor 2

Complement Receptor 2 (CR2), also known as CD21 (Cluster of Differentiation 21), is a protein that in humans is encoded by the CR2 gene. CR2 is a member of the complement system, which is part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane. It is involved in the immune response and is a receptor for C3d, C3dg, and iC3b complement fragments, as well as the Epstein-Barr virus (EBV).

Structure

CR2 is a type I transmembrane protein. It is primarily expressed on B cells, follicular dendritic cells, and some epithelial cells. The protein has a series of repeating units that are involved in its binding activities. These include short consensus repeats (SCRs) that are typical for proteins involved in the complement system.

Function

The main function of CR2 is to bind to complement fragments that have opsonized (coated) antigens, facilitating the immune response. By binding to C3d fragments on the surface of antigens, CR2 lowers the threshold for B cell activation and antibody production, essentially making it easier for the immune system to respond to threats. Additionally, CR2 is involved in the enhancement of antigen presentation and the regulation of B cell activation and survival.

CR2 also serves as a receptor for the Epstein-Barr virus, allowing it to infect B cells. This interaction is a critical step in the pathogenesis of EBV-related diseases, including infectious mononucleosis and certain types of cancer such as Burkitt's lymphoma.

Clinical Significance

Alterations in CR2 expression or function have been implicated in a variety of autoimmune diseases, such as Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The role of CR2 in these diseases is thought to be related to its involvement in the regulation of the immune response, where an imbalance or dysfunction can lead to autoimmunity.

Given its role in EBV infection, CR2 is also of interest in the study of EBV-associated malignancies. Therapeutic strategies targeting CR2 or its interactions with complement fragments and EBV are under investigation for the treatment of autoimmune diseases and prevention of EBV infection and its associated cancers.

Genetics

The CR2 gene is located on chromosome 1 in humans. Variants in the CR2 gene have been associated with susceptibility to autoimmune diseases, highlighting the importance of genetic factors in the regulation of the immune response and the development of autoimmunity.

Research Directions

Research on CR2 continues to focus on its role in the immune system, its interactions with pathogens like EBV, and its potential as a therapeutic target. Understanding the molecular mechanisms underlying CR2 function and its interactions with other components of the immune system may lead to new treatments for autoimmune diseases, infectious diseases, and cancers.