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

Cyril Planchais | Zendy; Ayrin Kök | Zendy; Alexia Kanyavuz | Zendy; Valérie Lorin | Zendy; Timothée Bruel | Zendy; Florence GuivelBenhassine | Zendy; Tim Rollenske | Zendy; Julie Prigent | Zendy; Thierry Hieu | Zendy; Thiérry Prazuck | Zendy; Laurent Lefrou | Zendy; Hedda Wardemann | Zendy; Olivier Schwartz | Zendy; Jordan D. Dimitrov | Zendy; Laurent Hocqueloux | Zendy; Hugo Mouquet | Zendy

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

Author(s) -

Cyril Planchais,

Ayrin Kök,

Alexia Kanyavuz,

Valérie Lorin,

Timothée Bruel,

Florence GuivelBenhassine,

Tim Rollenske,

Julie Prigent,

Thierry Hieu,

Thiérry Prazuck,

Laurent Lefrou,

Hedda Wardemann,

Olivier Schwartz,

Jordan D. Dimitrov,

Laurent Hocqueloux,

Hugo Mouquet

Publication year - 2019

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2019.03.032

Subject(s) - antibody , transcytosis , biology , glycoprotein , monoclonal antibody , gp41 , antigen , secretion , immune system , virology , immunology , antibody dependent cell mediated cytotoxicity , epitope , microbiology and biotechnology , receptor , biochemistry , endocytosis

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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