FcγR Binding and ADCC Activity of Human IgG Allotypes.
Antibody-Dependent Cell Cytotoxicity
Cells, Cultured
Glycosylation
Humans
Immunoglobulin Allotypes
/ metabolism
Immunoglobulin G
/ metabolism
Immunoglobulin Heavy Chains
/ genetics
Immunological Synapses
/ metabolism
Killer Cells, Natural
/ immunology
Polymorphism, Genetic
Protein Binding
Receptors, IgG
/ genetics
Fc gamma receptor
IgG polymorphism
antibodies
antibody dependent cellular cytotoxicity
glycosylation
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
17
01
2020
accepted:
01
04
2020
entrez:
22
5
2020
pubmed:
22
5
2020
medline:
18
3
2021
Statut:
epublish
Résumé
Antibody dependent cellular cytotoxicity (ADCC) is an Fc-dependent effector function of IgG important for anti-viral immunity and anti-tumor therapies. NK-cell mediated ADCC is mainly triggered by IgG-subclasses IgG1 and IgG3 through the IgG-Fc-receptor (FcγR) IIIa. Polymorphisms in the immunoglobulin gamma heavy chain gene likely form a layer of variation in the strength of the ADCC-response, but this has never been studied in detail. We produced all 27 known IgG allotypes and assessed FcγRIIIa binding and ADCC activity. While all IgG1, IgG2, and IgG4 allotypes behaved similarly within subclass, large allotype-specific variation was found for IgG3. ADCC capacity was affected by residues 291, 292, and 296 in the CH2 domain through altered affinity or avidity for FcγRIIIa. Furthermore, allotypic variation in hinge length affected ADCC, likely through altered proximity at the immunological synapse. Thus, these functional differences between IgG allotypes have important implications for therapeutic applications and susceptibility to infectious-, allo- or auto-immune diseases.
Identifiants
pubmed: 32435243
doi: 10.3389/fimmu.2020.00740
pmc: PMC7218058
doi:
Substances chimiques
FCGR3A protein, human
0
Immunoglobulin Allotypes
0
Immunoglobulin G
0
Immunoglobulin Heavy Chains
0
Receptors, IgG
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
740Informations de copyright
Copyright © 2020 de Taeye, Bentlage, Mebius, Meesters, Lissenberg-Thunnissen, Falck, Sénard, Salehi, Wuhrer, Schuurman, Labrijn, Rispens and Vidarsson.
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