Broadly neutralizing HIV-1 antibody identified in a lupus patient

Broadly neutralizing antibodies (BnAbs) represent a promising strategy for targeting rapidly mutating viruses, such as HIV-1. BnAbs recognize conserved epitopes and display unique characteristics that suggest that their development may be limited by immune tolerance. In this episode, Baton Haynes discusses the identification and characterization of a BnAb in an HIV-1-infected individual that developed the autoimmune disease systemic lupus erythematosus. The BnAb targeted both the HIV-1 envelope and human antigens, including dsDNA, supporting the hypothesis that lax immune control allows for maturation and production of BnAbs.

Published March 10, 2014, by The JCI

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An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1
Mattia Bonsignori, … , John R. Mascola, Barton F. Haynes
Mattia Bonsignori, … , John R. Mascola, Barton F. Haynes
Published April 1, 2014; First published March 10, 2014
Citation Information: J Clin Invest. 2014;124(4):1835-1843. https://doi.org/10.1172/JCI73441.
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Research Article Immunology

An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1

Abstract

Broadly HIV-1–neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated that HIV-1–infected individuals with autoimmune disease and defective immune tolerance mechanisms may produce BnAbs more readily than those without autoimmune diseases. In this study, we identified an HIV-1–infected individual with SLE who exhibited controlled viral load (<5,000 copies/ml) in the absence of controlling HLA phenotypes and developed plasma HIV-1 neutralization breadth. We collected memory B cells from this individual and isolated a BnAb, CH98, that targets the CD4 binding site (CD4bs) of HIV-1 envelope glycoprotein 120 (gp120). CH98 bound to human antigens including dsDNA, which is specifically associated with SLE. Anti-dsDNA reactivity was also present in the patient’s plasma. CH98 had a mutation frequency of 25% and 15% nt somatic mutations in the heavy and light chain variable domains, respectively, a long HCDR3, and a deletion in the light chain CDR1. The occurrence of anti-dsDNA reactivity by a HIV-1 CD4bs BnAb in an individual with SLE raises the possibility that some BnAbs and SLE-associated autoantibodies arise from similar pools of B cells.

Authors

Mattia Bonsignori, Kevin Wiehe, Sebastian K. Grimm, Rebecca Lynch, Guang Yang, Daniel M. Kozink, Florence Perrin, Abby J. Cooper, Kwan-Ki Hwang, Xi Chen, Mengfei Liu, Krisha McKee, Robert J. Parks, Joshua Eudailey, Minyue Wang, Megan Clowse, Lisa G. Criscione-Schreiber, M. Anthony Moody, Margaret E. Ackerman, Scott D. Boyd, Feng Gao, Garnett Kelsoe, Laurent Verkoczy, Georgia D. Tomaras, Hua-Xin Liao, Thomas B. Kepler, David C. Montefiori, John R. Mascola, Barton F. Haynes

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