Complement Is Activated by IgG Hexamers Assembled at the Cell Surface-Reference-Cited by-同舟云学术

Complement Is Activated by IgG Hexamers Assembled at the Cell Surface

Published:2014-03-14 Issue:6176 Volume:343 Page:1260-1263
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Diebolder Christoph A.¹²,Beurskens Frank J.³,de Jong Rob N.³,Koning Roman I.²,Strumane Kristin³,Lindorfer Margaret A.⁴,Voorhorst Marleen³,Ugurlar Deniz¹,Rosati Sara⁵,Heck Albert J. R.⁵,van de Winkel Jan G. J.³⁶,Wilson Ian A.⁷⁸,Koster Abraham J.²,Taylor Ronald P.⁴,Ollmann Saphire Erica⁹,Burton Dennis R.⁸⁹¹⁰,Schuurman Janine³,Gros Piet¹,Parren Paul W. H. I.³

Affiliation:

1. Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, 3584 CH Utrecht, Netherlands.

2. Department of Molecular Cell Biology, Electron Microscopy Section, Leiden University Medical Center, 2300 RC Leiden, Netherlands.

3. Genmab, 3584 CM Utrecht, Netherlands.

4. Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

5. Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CH Utrecht, Netherlands.

6. Department of Immunology, University Medical Center, 3584 CX Utrecht, Netherlands.

7. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

8. IAVI Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.

9. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.

10. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

Abstract

Hexing Complement 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. (p. 1260 ) 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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