Conserved FcγR- glycan discriminates between fucosylated and afucosylated IgG in humans and mice. (February 2018)

• Record Type: Journal Article
• Authors: Dekkers, Gillian; Bentlage, Arthur E.H.; Plomp, Rosina; Visser, Remco; Koeleman, Carolien A.M.; Beentjes, Anna; Mok, Juk Yee; van Esch, Wim J.E.; Wuhrer, Manfred; Rispens, Theo; Vidarsson, Gestur
• Is Part Of: Molecular immunology. Volume 94(2018:Feb.)
• Page Start: 54
• Page End: 60
• Publication Date: 2018-02
• Subjects: Asn asparagine -- Bisection bisecting GlcNAc -- Fc fragment crystallizable -- FcγR Fc gamma receptor -- GlcNAc N-acetylglucosamine -- HEK human embryonic kidney -- hFcγR human FcγR -- hIgG human IgG -- IgG immunoglobulin G -- mFcγR —mouse FcγR -- mIgG mouse IgG -- N162 asparagine at position 162 -- N162A asparagine at position 162 substituted by alanine -- N297A asparagine at position 297 substituted by alanine -- PBS phosphate buffered saline -- Rmax maximum response -- SPR surface plasmon resonance -- V158 valine at position 158 -- WT wild type; Fc gamma receptors -- N-Glycosylation -- Immunoglobulin -- Fucosylation -- Murine -- Human; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2017.12.006
• Languages: English
• ISSNs: 0161-5890

Abstract

Graphical abstract: Highlights: The N162 glycan is conserved between the orthologous human FcγRIIIa and mouse FcγRIV. This glycan endows the receptors to discriminate between fucosylated and afucosylated IgG. Human afucosylated IgG/FcγRIIIa affinity is further directed by additional galactosylation. Mouse afucosylated IgG/FcγRIV affinity remains unaffected by additional galactosylation. Abstract: The binding strength between IgG and FcγR is influenced by the composition of the N-linked glycan at position N297 in the Fc-domain of IgG. Particularly, afucosylation increases the binding affinity of human IgG1 to human FcγRIIIa up to ∼20 fold, and additional galactosylation of the afucosylated IgG increases the affinity up to ∼40 fold. The increase in affinity for afucosylated IgG has previously been shown to depend on direct carbohydrate-carbohydrate interactions between the IgG-Fc glycan with an N-linked glycan at position 162 unique to hFcγRIIIa and hFcγRIIIb. Here we report that the N162 glycosylation site is also found in the orthologous mouse FcγR, mFcγRIV. The N162-glycan in mFcγRIV was also responsible for enhancing the binding to mouse IgG with reduced fucose similar to hFcγRIIIa. However, unlike hFcγRIIIa, mFcγRIV did not bind more avidly to IgG with increased galactose and reduced fucose. Overall, these results suggest the N162-glycan in the human FcγRIII family and its orthologous mouse FcγRIV to be functionally conserved.