Generic placeholder image

Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

The Structure-Function Relationships of Complement Receptor Type 2 (CR2; CD21)

Author(s): Jonathan Paul Hannan

Volume 17, Issue 5, 2016

Page: [463 - 487] Pages: 25

DOI: 10.2174/1389203717666151201192124

Price: $65

Abstract

Human complement receptor type 2 (CR2; CD21) is a surface-associated glycoprotein which binds to a variety of endogenous ligands, including the complement component C3 fragments iC3b, C3dg and C3d, the low-affinity IgE receptor CD23, and the type I cytokine, interferon-alpha. CR2 links the innate complement-mediated immune response to pathogens and foreign antigens with the adaptive immune response by binding to C3d that is covalently attached to targets, and which results in a cell signalling phenomenon that lowers the threshold for B cell activation. Variations or deletions of the CR2 gene in humans, or the Cr2 gene in mice associate with a variety of autoimmune and inflammatory conditions. A number of infectious agents including Epstein-Barr virus (EBV), Human Immunodeficiency Virus (HIV) and prions also bind to CR2 either directly or indirectly by means of C3d-targeted immune complexes.

In this review we discuss the interactions that CR2 undertakes with its best characterized ligands C3d, CD23 and the EBV gp350/220 envelope protein. To date only a single physiologically relevant complex of CR2 with one of its ligands, C3d, has been elucidated. By contrast, the interactions with CD23 and EBV gp350/220, while being important from physiologic and disease-associated standpoints, respectively, are only incompletely understood. A detailed knowledge of the structure-function relationships that CR2 undergoes with its ligands is necessary to understand the implications of using recombinant CR2 in therapeutic or imaging agents, or alternatively targeting CR2 to down-regulate the antibody mediated immune response in cases of autoimmunity.

Keywords: Complement receptor type 2, innate immunity, autoimmunity, complement C3d, structure-function relationships, B cell signalling, regulators of complement activation.

Graphical Abstract

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy