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

Related articles

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 March 10, 2014
Citation Information: J Clin Invest. 2014;124(4):1835-1843. https://doi.org/10.1172/JCI73441.
View: Text | PDF
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

×
Advertisement