1. An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1
- Author
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Bonsignori, Mattia, Wiehe, Kevin, Grimm, Sebastian K., Lynch, Rebecca, Yang, Guang, Kozink, Daniel M., Perrin, Florence, Cooper, Abby J., Hwang, Kwan-Ki, Chen, Xi, Liu, Mengfei, McKee, Krisha, Parks, Robert J., Eudailey, Joshua, Wang, Minyue, Clowse, Megan, Criscione-Schreiber, Lisa G., Moody, M. Anthony, Ackerman, Margaret E., Boyd, Scott D., Gao, Feng, Kelsoe, Garnett, Verkoczy, Laurent, Tomaras, Georgia D., Liao, Hua-Xin, Kepler, Thomas B., Montefiori, David C., Mascola, John R., and Haynes, Barton F.
- Subjects
Autoantibodies -- Identification and classification -- Physiological aspects -- Research ,Systemic lupus erythematosus -- Genetic aspects -- Research ,Immunological tolerance -- Research ,HIV infection -- Genetic aspects -- Research ,Health care industry - 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., Introduction Broadly HIV-1-neutralizing antibodies (BnAbs) have been isolated that bind to multiple epitopes on the envelope glycoproteins gp120 and gp41 (reviewed in ref. 1). 2G12 recognizes a posttranslational glycan epitope [...]
- Published
- 2014
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