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Complement is activated by IgG hexamers assembled at the cell surface

Item Type:Article
Title:Complement is activated by IgG hexamers assembled at the cell surface
Creators Name:Diebolder, C.A. and Beurskens, F.J. and de Jong, R.N. and Koning, R.I. and Strumane, K. and Lindorfer, M.A. and Voorhorst, M. and Ugurlar, D. and Rosati, S. and Heck, A.J.R. and van de Winkel, J.G.J. and Wilson, I.A. and Koster, A.J. and Taylor, R.P. and Saphire, E.O. and Burton, D.R. and Schuurman, J. and Gros, P. and Parren, P.W.H.I
Abstract:Complement activation by antibodies bound to pathogens, tumors, and self antigens is a critical feature of natural immune defense, a number of disease processes, and immunotherapies. How antibodies activate the complement cascade, however, is poorly understood. We found that specific noncovalent interactions between Fc segments of immunoglobulin G (IgG) antibodies resulted in the formation of ordered antibody hexamers after antigen binding on cells. These hexamers recruited and activated C1, the first component of complement, thereby triggering the complement cascade. The interactions between neighboring Fc segments could be manipulated to block, reconstitute, and enhance complement activation and killing of target cells, using all four human IgG subclasses. We offer a general model for understanding antibody-mediated complement activation and the design of antibody therapeutics with enhanced efficacy.
Keywords:Cell Membrane, Complement Activation, Complement C1, Immunoglobulin Fab Fragments, Immunoglobulin G, Liposomes, Protein Conformation, Protein Multimerization
Publisher:American Association for the Advancement of Science
Page Range:1260-3
Date:14 March 2014
Official Publication:https://doi.org/10.1126/science.1248943
PubMed:View item in PubMed

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