Immunologic characteristics of HIV-infected individuals who make broadly neutralizing antibodies |
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Authors: | Persephone Borrow M. Anthony Moody |
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Affiliation: | 1. Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK;2. Duke University Human Vaccine Institute and Departments of Pediatrics and Immunology, Duke University School of Medicine, Durham, NC, USA |
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Abstract: | Induction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV-1) is a key, as-yet-unachieved goal of prophylactic HIV-1 vaccine strategies. However, some HIV-infected individuals develop bnAbs after approximately 2-4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy-chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV-1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV-1 vaccine design. |
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Keywords: | autoantibody broadly neutralizing antibody CD4+ T follicular helper cell CD4+ T follicular regulatory cell human immunodeficiency virus regulatory T cell |
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