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HIV-1 Envelope Recognition by Polyreactive and Cross-Reactive Intestinal B Cells

Mucosal immune responses to HIV-1 involve the recognition of the viral envelope glycoprotein (gp)160 by tissue-resident B cells and subsequent secretion of antibodies. To characterize the B cells “sensing” HIV-1 in the gut of infected individuals, we probed monoclonal antibodies produced from single...

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Detalles Bibliográficos
Autores principales: Planchais, Cyril, Kök, Ayrin, Kanyavuz, Alexia, Lorin, Valérie, Bruel, Timothée, Guivel-Benhassine, Florence, Rollenske, Tim, Prigent, Julie, Hieu, Thierry, Prazuck, Thierry, Lefrou, Laurent, Wardemann, Hedda, Schwartz, Olivier, Dimitrov, Jordan D., Hocqueloux, Laurent, Mouquet, Hugo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458971/
https://www.ncbi.nlm.nih.gov/pubmed/30970259
http://dx.doi.org/10.1016/j.celrep.2019.03.032
Descripción
Sumario:Mucosal immune responses to HIV-1 involve the recognition of the viral envelope glycoprotein (gp)160 by tissue-resident B cells and subsequent secretion of antibodies. To characterize the B cells “sensing” HIV-1 in the gut of infected individuals, we probed monoclonal antibodies produced from single intestinal B cells binding to recombinant gp140 trimers. A large fraction of mucosal B cell antibodies were polyreactive and showed only low affinity to HIV-1 envelope glycoproteins, particularly the gp41 moiety. A few high-affinity gp140 antibodies were isolated but lacked neutralizing, potent ADCC, and transcytosis-blocking capacities. Instead, they displayed cross-reactivity with defined self-antigens. Specifically, intestinal HIV-1 gp41 antibodies targeting the heptad repeat 2 region (HR2) cluster II cross-reacted with the p38α mitogen-activated protein kinase 14 (MAPK14). Hence, physiologic polyreactivity of intestinal B cells and molecular mimicry-based self-reactivity of HIV-1 antibodies are two independent phenomena, possibly diverting and/or impairing mucosal humoral immunity to HIV-1.