An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1.
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.
Clowse, Megan Elizabeth Bowles
Criscione-Schreiber, Lisa Giorgina
Haynes, Barton Ford
Kelsoe, Garnett H.
Montefiori, David Charles
Moody, Michael Anthony
Tomaras, Georgia Doris
Verkoczy, Laurent Karl
Wiehe, Kevin J
Bonsignori, M; Wiehe, K; Grimm, SK; Lynch, R; Yang, G; Kozink, DM; Perrin, F; Cooper, AJ; Hwang, K-K; Chen, X; Liu, M; McKee, K; Parks, RJ; Eudailey, J; Wang, M; Clowse, M; Criscione-Schreiber, LG; Moody, MA; Ackerman, ME; Boyd, SD; Gao, F; Kelsoe, G; Verkoczy, L; Tomaras, GD; Liao, H-X; Kepler, TB; Montefiori, DC; Mascola, JR; Haynes, BF
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