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- Title
An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1.
- Authors
Bonsignori, Mattia; Wiehe, Kevin; Grimm, Sebastian K.; Lynch, Rebecca; Guang Yang; Kozink, Daniel M.; Perrin, Florence; Cooper, Abby J.; Kwan-Ki Hwang; Xi Chen; Mengfei Liu; McKee, Krisha; Parks, Robert J.; Eudailey, Joshua; Minyue Wang; Clowse, Megan; Criscione-Schreiber, Lisa G.; Moody, M. Anthony; Ackerman, Margaret E.; Boyd, Scott D.
- 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 (gpl20). 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.
- Subjects
IMMUNOGLOBULINS; HIV infections -- Immunological aspects; ANTIGENS; AUTOANTIBODIES; HIV
- Publication
Journal of Clinical Investigation, 2014, Vol 124, Issue 4, p1835
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI73441