A MUC16 IgG Binding Activity Selects for a Restricted Subset of IgG Enriched for Certain Simian Immunodeficiency Virus Epitope Specificities.
SIV infection
antibodies
mucosal immunology
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
14 02 2020
14 02 2020
Historique:
received:
29
07
2019
accepted:
09
11
2019
pubmed:
30
11
2019
medline:
22
8
2020
entrez:
29
11
2019
Statut:
epublish
Résumé
We have recently shown that MUC16, a component of the glycocalyx of some mucosal barriers, has elevated binding to the G0 glycoform of the Fc portion of IgG. Therefore, IgG from patients chronically infected with human immunodeficiency virus (HIV), who typically exhibit increased amounts of G0 glycoforms, showed increased MUC16 binding compared to uninfected controls. Using the rhesus macaque simian immunodeficiency virus SIVmac251 model, we can compare plasma antibodies before and after chronic infection. We find increased binding of IgG to MUC16 after chronic SIV infection. Antibodies isolated for tight association with MUC16 (MUC16-eluted antibodies) show reduced FcγR engagement and antibody-dependent cellular cytotoxicity (ADCC) activity. The glycosylation profile of these IgGs was consistent with a decrease in FcγR engagement and subsequent ADCC effector function, as they contain a decrease in afucosylated bisecting glycoforms that preferentially bind FcγRs. Testing of the SIV antigen specificity of IgG from SIV-infected macaques revealed that the MUC16-eluted antibodies were enriched for certain specific epitopes, including regions of gp41 and gp120. This enrichment of specific antigen responses for fucosylated bisecting glycoforms and the subsequent association with MUC16 suggests that the immune response has the potential to direct specific epitope responses to localize to the glycocalyx through interaction with this specific mucin.
Identifiants
pubmed: 31776284
pii: JVI.01246-19
doi: 10.1128/JVI.01246-19
pmc: PMC7022352
pii:
doi:
Substances chimiques
AIDS Vaccines
0
Antibodies, Viral
0
CA-125 Antigen
0
Epitopes
0
Immunoglobulin G
0
MUC16 protein, human
0
Membrane Proteins
0
Mucins
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 : P01 AI120756
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI125171
Pays : United States
Organisme : NIH HHS
ID : K01 OD026571
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM108569
Pays : United States
Organisme : NIH HHS
ID : P51 OD011104
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI124912
Pays : United States
Organisme : NIH HHS
ID : K01 OD024882
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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