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

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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 | Hocqueloux, Laurent | Mouquet, Hugo

Edité par CCSD ; Elsevier Inc -

International audience. 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.

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