Editors' ChoiceImmunology

Hexing Complement

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Sci. Signal.  18 Mar 2014:
Vol. 7, Issue 317, pp. ec74
DOI: 10.1126/scisignal.2005278

Complement activation is an immediate and potent immune defense mechanism, but how immunoglobulin G (IgG) antibodies activate complement at the molecular level is poorly understood. Using high-resolution crystallography, Diebolder et al. show that human IgGs form hexameric structures by interacting with neighboring IgG molecules, and the complex then activates complement. Thus, IgG molecules and the complement system can coexist in the blood because complement activation will only be triggered after IgG senses a surface antigen and starts to aggregate.

C. A. Diebolder, F. J. Beurskens, R. N. de Jong, R. I. Koning, K. Strumane, M. A. Lindorfer, M. Voorhorst, D. Ugurlar, S. Rosati, A. J. R. Heck, J. G. J. van de Winkel, I. A. Wilson, A. J. Koster, R. P. Taylor, E. O. Saphire, D. R. Burton, J. Schuurman, P. Gros, P. W. H. I. Parren, Complement is activated by IgG hexamers assembled at the cell surface. Science 343, 1260–1263 (2014). [Abstract] [Full Text]