Two Families of Env Antibodies Efficiently Engage Fc-Gamma Receptors and Eliminate HIV-1-Infected Cells.
Antibody-Dependent Cell Cytotoxicity
Binding Sites
Epitopes
/ immunology
HIV Antibodies
/ immunology
HIV Infections
/ immunology
HIV-1
/ immunology
Humans
Protein Binding
Receptors, IgG
/ immunology
Recombinant Proteins
/ immunology
T-Lymphocytes
/ immunology
env Gene Products, Human Immunodeficiency Virus
/ immunology
ADCC
CD4-mimetics
Env
FcγRIIIa
HIV-1
anti-cluster A antibodies
anti-coreceptor binding site antibodies
nonneutralizing antibodies
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
01 02 2019
01 02 2019
Historique:
received:
11
10
2018
accepted:
07
11
2018
pubmed:
16
11
2018
medline:
9
11
2019
entrez:
16
11
2018
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30429344
pii: JVI.01823-18
doi: 10.1128/JVI.01823-18
pmc: PMC6340017
pii:
doi:
Substances chimiques
Epitopes
0
FCGR3A protein, human
0
HIV Antibodies
0
Receptors, IgG
0
Recombinant Proteins
0
env Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI116274
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI129769
Pays : United States
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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