C1q binding to surface-bound IgG is stabilized by C1r <sub>2</sub> s <sub>2</sub> proteases
Seline A. Zwarthoff, Kevin Widmer, Annemarie Kuipers, Jürgen Strasser, Maartje Ruyken, Piet C. Aerts, Carla J. C. de Haas, Deniz Ugurlar, Maurits A. den Boer, Gestur Vidarsson, Jos A. G. van Strijp, Piet Gros, Paul W.H.I. Parren, Kok P. M. van Kessel, Johannes Preiner, Frank J. Beurskens, Janine Schuurman, Daniel Ricklin, Suzan H. M. Rooijakkers
Abstract
Significance Antibody-dependent complement activation plays a major role in various pathophysiological processes in our body, including infection, inflammation, autoimmunity, and transplant rejection. In order to activate complement, antibodies should bind to target cells and recruit complement component C1. C1 is a large, multimolecular complex that consists of the antibody recognition protein C1q and a heterotetramer of proteases (C1r 2 s 2 ). Although it is believed that interactions between C1 and IgGs are solely mediated by C1q, we here show that C1r 2 s 2 proteases affect the capacity of C1q to form an avid complex with surface-bound IgG molecules. Furthermore, we demonstrate that C1q–IgG stability is influenced by IgG oligomerization and that promoting IgG oligomerization improves phagocytosis of the pathogenic bacterium Staphylococcus aureus .