Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation

Hugo Mouquet, Johannes F. Scheid, Markus J. Zoller, Michelle Krogsgaard, Rene G. Ott, Shetha Shukair, Maxim N. Artyomov, John Pietzsch, Mark Connors, Florencia Pereyra, Bruce D. Walker, David D. Ho, Patrick C. Wilson, Michael S. Seaman, Herman N. Eisen, Arup K. Chakraborty, Thomas J. Hope, Jeffrey V. Ravetch, Hedda Wardemann and Michel C. Nussenzweig ()
Additional contact information
Hugo Mouquet: Laboratory of Molecular Immunology, The Rockefeller University
Johannes F. Scheid: Laboratory of Molecular Immunology, The Rockefeller University
Markus J. Zoller: Max Planck Institute for Infection Biology
Michelle Krogsgaard: New York University School of Medicine
Rene G. Ott: Laboratory of Molecular Genetics and Immunology, The Rockefeller University
Shetha Shukair: Northwestern University
Maxim N. Artyomov: Chemical Engineering, Biology, and Biological Engineering, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
John Pietzsch: Laboratory of Molecular Immunology, The Rockefeller University
Mark Connors: Laboratory of Immunoregulation, and Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health
Florencia Pereyra: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard Medical School
Bruce D. Walker: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard Medical School
David D. Ho: Aaron Diamond AIDS Research Center
Patrick C. Wilson: Section of Rheumatology, University of Chicago
Michael S. Seaman: Beth Israel Deaconess Medical Center
Herman N. Eisen: Chemical Engineering, Biology, and Biological Engineering, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
Arup K. Chakraborty: Chemical Engineering, Biology, and Biological Engineering, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
Thomas J. Hope: Northwestern University
Jeffrey V. Ravetch: Laboratory of Molecular Genetics and Immunology, The Rockefeller University
Hedda Wardemann: Max Planck Institute for Infection Biology
Michel C. Nussenzweig: Laboratory of Molecular Immunology, The Rockefeller University

Nature, 2010, vol. 467, issue 7315, 591-595

Abstract: Antibodies hedge their bets Most antibodies are highly specific, binding with high affinity to a single foreign antigen. However, an analysis of human immunodeficiency virus (HIV) envelope glycoprotein-specific monoclonal antibodies from infected subjects provides evidence for a surprisingly high degree of polyreactivity. Of 134 different antibodies directed at the gp140 envelope glycoprotein cloned from six patients, 75% were polyreactive, binding with high affinity to one gp140 site and with lower affinity to other sites on the viral surface. Relatively few gp140 glycoprotein spikes are displayed on the surface of HIV, so homotypic bivalent antibody binding is disfavoured and 'heteroligation' may help to improve net antibody affinity in such instances.

Date: 2010
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DOI: 10.1038/nature09385

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