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Front. Immunol. | doi: 10.3389/fimmu.2018.00244

IgA targeting HIV-1 envelope gp41 triggers antibody-dependent cell cytotoxicity cross-clade and cooperates with gp41 specific IgG to increase cell lysis

  • 1Cell Biology and Host Pathogen interactions, Institut National de la Santé et de la Recherche Médicale (INSERM), France

The protective efficacy of Human Immunodeficiency Virus (HIV-1) antibodies (Ab) remains mostly correlated with their in vitro neutralizing activity engaging their Fab region. However, anti-HIV-1 Abs mediate also a broad array of Fc-mediated effector functions including antibody-dependent cell cytotoxicity (ADCC), that depend primarily on the Ab isotype. While ADCC is commonly associated with HIV-1 gp120 envelope-specific IgGs, whether IgAs, especially those targeting the HIV-1 gp41 envelope, also mediate ADCC remains elusive. Therefore, to assess the capacity of IgA specific for HIV-1 to induce Fcα-mediated ADCC, we used the gp41 envelope-specific IgA transformed from the neutralizing 2F5-IgG we have previously reported to induce ADCC. We demonstrate that 2F5-IgA engages FcαRI (CD89), expressed on human monocytes used as effector cells, to induce the lysis of HIV-1 Clade A and B infected target cells by ADCC. Furthermore, the 2F5-IgA and 2F5-IgG cooperate to enhance target-cells lysis by ADCC. Cooperation in ADCC is also observed between 2F5-IgA and the broadly neutralizing 10E8-IgG. These results provide a new perspective for IgA in protection against HIV-1 acquisition or reservoir eradication, and suggest that inducing IgA by vaccination, in particular when targeting gp41, in combination with IgG could strengthen protection by complementary and cooperative activities with IgG.

Keywords: ADCC, IgA, HIV-1, HIV Envelope Protein gp41, mucosal immune system

Received: 25 Sep 2017; Accepted: 29 Jan 2018.

Edited by:

Mario (. Clerici, Università degli Studi di Milano, Italy

Reviewed by:

Ann J. Hessell, Oregon Health & Science University, United States
Mara Biasin, Università degli Studi di Milano, Italy  

Copyright: © 2018 Duchemin, Khamassi, Xu, Tudor and Bomsel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Morgane Bomsel, Institut National de la Santé et de la Recherche Médicale (INSERM), Cell Biology and Host Pathogen interactions, 22 ue Mechain, Paris, 75014, France, morgane.bomsel@inserm.fr