PMID- 32222585
OWN - NLM
STAT- MEDLINE
DCOM- 20200713
LR  - 20200713
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 121
DP  - 2020 May
TI  - Glycosylation of Fcgamma receptors influences their interaction with various IgG1 
      glycoforms.
PG  - 144-158
LID - S0161-5890(19)30895-8 [pii]
LID - 10.1016/j.molimm.2020.03.010 [doi]
AB  - Most of therapeutic monoclonal antibodies belong to the immunoglobulin G1 (IgG1) 
      family; they interact with the Fcgamma receptors (FcgammaRs) at the surface of immune 
      cells to trigger effector functions. The IgG1-Fc N-glycans impact the interaction 
      with FcgammaRs and are considered a critical quality attribute. Pioneer studies on 
      FcgammaR N-glycans have unveiled an additional complexity in that the N-glycan linked 
      on the Asn-162 of FcgammaRIIIa was shown to be directly involved in the strong 
      affinity for afucosylated IgG1. The last few years have thus seen the emergence 
      of many studies investigating the complex influence of FcgammaRIIIa N-glycans on the 
      interaction with IgG1 through their glycosylation sites or their glycoprofiles. 
      In this context, we performed site-directed mutagenesis along with 
      glycoengineering on FcgammaRs (FcgammaRI, FcgammaRIIa(H131)/b and FcgammaRIIIa(V158/F158)) in an 
      effort to elucidate the impact of FcgammaRs N-glycans on the interaction with IgG1. 
      Furthermore, we assessed their binding to various trastuzumab glycoforms with an 
      enhanced surface plasmon resonance assay. The FcgammaRIIIa N-glycans had the highest 
      impact on the interaction with IgG1. More specifically, the N162 glycan 
      positively influenced the affinity (15-fold) for afucosylated IgG1 while the N45 
      glycan presented a negative impact (2-fold) regardless of the IgG1 glycoforms. 
      Interestingly, only the FcgammaRIIIa glycoprofile had an impact on the interaction 
      with IgG1 with a 1.5-fold affinity increase when FcgammaRIIIa displays high-mannose 
      glycans. These results provide invaluable insights into the complex and strong 
      influence of N-glycosylation upon FcgammaRs/IgG1 binding and are instrumental to 
      further understand the impact of FcgammaRs N-glycosylation in their natural forms.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Cambay, Florian
AU  - Cambay F
AD  - Department of Chemical Engineering, Polytechnique Montreal, Montreal, Canada; 
      Human Health Therapeutics Research Centre, National Research Council of Canada, 
      Montreal, Canada.
FAU - Forest-Nault, Catherine
AU  - Forest-Nault C
AD  - Department of Chemical Engineering, Polytechnique Montreal, Montreal, Canada; 
      Human Health Therapeutics Research Centre, National Research Council of Canada, 
      Montreal, Canada.
FAU - Dumoulin, Lea
AU  - Dumoulin L
AD  - Department of Chemical Engineering, Polytechnique Montreal, Montreal, Canada.
FAU - Seguin, Alexis
AU  - Seguin A
AD  - Department of Chemical Engineering, Polytechnique Montreal, Montreal, Canada.
FAU - Henry, Olivier
AU  - Henry O
AD  - Department of Chemical Engineering, Polytechnique Montreal, Montreal, Canada.
FAU - Durocher, Yves
AU  - Durocher Y
AD  - Human Health Therapeutics Research Centre, National Research Council of Canada, 
      Montreal, Canada; Department of Biochemistry and Molecular Medicine, University 
      of Montreal, Montreal, Canada. Electronic address: yves.durocher@nrc.gc.ca.
FAU - De Crescenzo, Gregory
AU  - De Crescenzo G
AD  - Department of Chemical Engineering, Polytechnique Montreal, Montreal, Canada. 
      Electronic address: gregory.decrescenzo@polymtl.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200326
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (FCGR1A protein, human)
RN  - 0 (FCGR2A protein, human)
RN  - 0 (FCGR2B protein, human)
RN  - 0 (FCGR3A protein, human)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Polysaccharides)
RN  - 0 (Protein Isoforms)
RN  - 0 (Receptors, IgG)
RN  - PHA4727WTP (Mannose)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Cricetulus
MH  - Glycosylation
MH  - HEK293 Cells
MH  - Humans
MH  - Immunoglobulin G/immunology/*metabolism
MH  - Mannose/metabolism
MH  - Mutagenesis, Site-Directed
MH  - Polysaccharides/metabolism
MH  - Protein Engineering
MH  - Protein Isoforms/genetics/immunology/metabolism
MH  - Receptors, IgG/genetics/immunology/*metabolism
OTO - NOTNLM
OT  - Fc-gamma receptor
OT  - IgG
OT  - N-linked glycosylation
OT  - Protein-protein interaction
OT  - SPR
OT  - Site-directed mutagenesis
COIS- Declaration of Competing Interest The authors declare that they have no conflicts 
      of interest with the contents of this article.
EDAT- 2020/03/31 06:00
MHDA- 2020/07/14 06:00
CRDT- 2020/03/31 06:00
PHST- 2019/12/16 00:00 [received]
PHST- 2020/02/26 00:00 [revised]
PHST- 2020/03/16 00:00 [accepted]
PHST- 2020/03/31 06:00 [pubmed]
PHST- 2020/07/14 06:00 [medline]
PHST- 2020/03/31 06:00 [entrez]
AID - S0161-5890(19)30895-8 [pii]
AID - 10.1016/j.molimm.2020.03.010 [doi]
PST - ppublish
SO  - Mol Immunol. 2020 May;121:144-158. doi: 10.1016/j.molimm.2020.03.010. Epub 2020 
      Mar 26.