title: The Structure-Function Relationships of Complement Receptor Type 2 (CR2; CD21).
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.
authors.affiliation: Division of Rheumatology, Mail Stop B-115, Department of Medicine, Barbara Davis Center for Childhood Diabetes, Anschutz Medical Campus, University of Colorado Denver, 1775 Aurora Court, Aurora CO 80045, USA. Jonathan.Hannan@ucdenver.edu.
authors.forename: Jonathan Paul
authors.initials: JP
authors.lastname: Hannan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity; D001665:Binding Sites; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D005810:Multigene Family; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D017464:Receptors, Complement 3d / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D017464:Receptors, Complement 3d; D003165:Complement System Proteins