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Two Families of Env Antibodies Efficiently Engage Fc-Gamma Receptors and Eliminate HIV-1-Infected Cells.
- Source :
-
Journal of virology [J Virol] 2019 Jan 17; Vol. 93 (3). Date of Electronic Publication: 2019 Jan 17 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- HIV-1 conceals epitopes of its envelope glycoproteins (Env) recognized by antibody (Ab)-dependent cellular cytotoxicity (ADCC)-mediating antibodies. These Abs, including anti-coreceptor binding site (CoRBS) and anti-cluster A antibodies, preferentially recognize Env in its "open" conformation. The binding of anti-CoRBS Abs has been shown to induce conformational changes that further open Env, allowing interaction of anti-cluster A antibodies. We explored the possibility that CoRBS Abs synergize with anti-cluster A Abs to engage Fc-gamma receptors to mediate ADCC. We found that binding of anti-CoRBS and anti-cluster A Abs to the same gp120 is required for interaction with soluble dimeric FcγRIIIa in enzyme-linked immunosorbent assays (ELISAs). We also found that Fc regions of both Abs are required to optimally engage FcγRIIIa and mediate robust ADCC. Taken together, our results indicate that these two families of Abs act together in a sequential and synergistic fashion to promote FcγRIIIa engagement and ADCC. IMPORTANCE The "open" CD4-bound conformation of HIV-1 envelope glycoproteins is the primary target of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies present in HIV-positive (HIV <superscript>+</superscript> ) sera, such as anti-coreceptor binding site and anti-cluster A antibodies. Here we report that the binding of these two families of antibodies is required to engage FcγRIIIa and mediate ADCC.<br /> (Copyright © 2019 American Society for Microbiology.)
- Subjects :
- Antibody-Dependent Cell Cytotoxicity
Binding Sites
HIV Antibodies metabolism
HIV Infections immunology
HIV Infections virology
Humans
Protein Binding
Receptors, IgG immunology
Recombinant Proteins immunology
Epitopes immunology
HIV Antibodies immunology
HIV Infections prevention & control
HIV-1 immunology
Receptors, IgG metabolism
T-Lymphocytes immunology
env Gene Products, Human Immunodeficiency Virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 93
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 30429344
- Full Text :
- https://doi.org/10.1128/JVI.01823-18