Abstract: The homing of lymphocytes to the mucosa is mainly controlled by α4β7 integrin, and it is amplified during gut chronic inflammation, as occurs with HIV and/or inflammatory bowel diseases. We designed and applied an improved immunization strategy based on an innovative selection process to isolate new α4β7+ lymphocyte–specific monoclonal antibodies that are able to prevent their migration into inflamed gut tissues and/or to counteract HIV infection in vitro. First, 5 monoclonal antibodies (1 IgA, 1 IgM, and 4 IgGs) were selected based on their capacity to recognize α4 or β7 homodimers and α4β7 heterodimers in transfected human cells. Their ability to block gp120/α4β7 or MAdCAM-1/α4β7 interactions was then measured in vitro with human T and B lymphocytes. In vitro, the anti-α4β7 IgA isotype was found to have the highest affinity for the α4β7 heterodimer, and it significantly reduced HIV replication in retinoic acid–treated α4β7hi CD4+ human T cells. This α4β7-specific IgA also displayed a high avidity for human and mouse α4β7+ lymphocytes in both mouse and human inflammatory colitis tissues. These new antibodies, and in particular those with mucosa-targeting isotypes such as IgA, could therefore be potential novel therapeutic tools for treating HIV and inflammatory bowel disease.
*GIMAP/EA3064, Université de Lyon, Saint-Etienne, France;
†NIH/NIAID Laboratory of Immunoregulation, Bethesda, MD;
‡Institut de Biologie et Chimie des Protéines, FRE3310/CNRS, Universités de Lyon, Lyon, France; and
§Dendritics SA, Lyon, France.
Correspondence to: Stéphane Paul, PhD, GIMAP EA3064, CIC1408, Laboratoire d'Immunologie CHU Saint-Etienne, Universités de Lyon, Saint-Etienne, France (e-mail: email@example.com).
A.G. was supported by a doctoral fellowship from Region Rhone-Alpes (France). This work was financed by research grants from Region Rhone-Alpes, ANRS, and Sidaction.
The authors have no conflicts of interest to disclose.
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Received December 02, 2016
Accepted January 23, 2017