title: Characterization of human complement receptor type 2 (CR2/CD21) as a receptor for IFN-alpha: a potential role in systemic lupus erythematosus.
abstract: Human complement receptor type 2 (CR2/CD21) is a B lymphocyte membrane glycoprotein that plays a central role in the immune responses to foreign Ags as well as the development of autoimmunity to nuclear Ags in systemic lupus erythematosus. In addition to these three well-characterized ligands, C3d/iC3b, EBV-gp350, and CD23, a previous study has identified CR2 as a potential receptor for IFN-alpha. IFN-alpha, a multifunctional cytokine important in the innate immune system, has recently been proposed to play a major pathogenic role in the development of systemic lupus erythematosus in humans and mice. In this study, we have shown using surface plasmon resonance and ELISA approaches that CR2 will bind IFN-alpha in the same affinity range as the other three well-characterized ligands studied in parallel. In addition, we show that IFN-alpha interacts with short consensus repeat domains 1 and 2 in a region that serves as the ligand binding site for C3d/iC3b, EBV-gp350, and CD23. Finally, we show that treatment of purified human peripheral blood B cells with the inhibitory anti-CR2 mAb 171 diminishes the induction of IFN-alpha-responsive genes. Thus, IFN-alpha represents a fourth class of extracellular ligands for CR2 and interacts with the same domain as the other three ligands. Defining the role of CR2 as compared with the well-characterized type 1 IFN-alpha receptor 1 and 2 in mediating innate immune and autoimmune roles of this cytokine should provide additional insights into the biologic roles of this interaction.
authors.affiliation: Department of Medicine and Department of Immunology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
authors.forename: Rengasamy
authors.initials: R
authors.lastname: Asokan
authors.forename: Jing
authors.initials: J
authors.lastname: Hua
authors.forename: Kendra A
authors.initials: KA
authors.lastname: Young
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Gould
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Hannan
authors.forename: Damian M
authors.initials: DM
authors.lastname: Kraus
authors.forename: Gerda
authors.initials: G
authors.lastname: Szakonyi
authors.forename: Gabrielle J
authors.initials: GJ
authors.lastname: Grundy
authors.forename: Xiaojiang S
authors.initials: XS
authors.lastname: Chen
authors.forename: Mary K
authors.initials: MK
authors.lastname: Crow
authors.forename: V Michael
authors.initials: VM
authors.lastname: Holers
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D001667:Binding, Competitive; D002478:Cells, Cultured; D015933:Complement C3d / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016898:Interferon-alpha / Q000378:metabolism*; D008024:Ligands; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D064547:Myxovirus Resistance Proteins; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017464:Receptors, Complement 3d / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017455:Receptors, IgE / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism; D020349:Surface Plasmon Resonance; D014763:Viral Matrix Proteins / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; C494651:DNAJC3 protein, human; C034059:GP 300-350, Epstein-Barr virus; D050956:HSP40 Heat-Shock Proteins; D016898:Interferon-alpha; D008024:Ligands; D008562:Membrane Glycoproteins; D064547:Myxovirus Resistance Proteins; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; D012965:Sodium Chloride; D015933:Complement C3d; D019204:GTP-Binding Proteins