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Article Dans Une Revue Cell Reports Année : 2019

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

Timothée Bruel
Florence Guivel-Benhassine
Thierry Hieu
Olivier Schwartz
  • Fonction : Auteur
  • PersonId : 999827

Résumé

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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Dates et versions

hal-02102470 , version 1 (17-04-2019)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Cyril Planchais, Ayrin Kök, Alexia Kanyavuz, Valérie Lorin, Timothée Bruel, et al.. HIV-1 Envelope Recognition by Polyreactive and Cross-Reactive Intestinal B Cells. Cell Reports, 2019, 27 (2), pp.572-585.e7. ⟨10.1016/j.celrep.2019.03.032⟩. ⟨hal-02102470⟩
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