Campus Units

Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of

Document Type

Article

Publication Version

Published Version

Publication Date

10-26-2018

Journal or Book Title

Journal of Biological Chemistry

Volume

293

Issue

43

First Page

16842

Last Page

16850

DOI

10.1074/jbc.RA118.004998

Abstract

Fc γ receptors (FcγRs) bind circulating IgG (IgG1) at the surface of leukocytes. Antibodies clustered at the surface of a targeted particle trigger a protective immune response through activating FcγRs. Three recent reports indicate that the composition of the asparagine-linked carbohydrate chains (N-glycans) of FcγRIIIa/CD16a impacted IgG1-binding affinity. Here we determined how N-glycan composition affected the affinity of the “low-affinity” FcγRs for six homogeneous IgG1 Fc N-glycoforms (G0, G0F, G2, G2F, A2G2, and A2G2F). Surprisingly, CD16a with oligomannose N-glycans bound to IgG1 Fc (A2G2) with a KD = 1.0 ± 0.1 nM. This affinity represents a 51-fold increase over the affinity measured for CD16a with complex-type N-glycans (51 ± 8 nM) and is comparable with the affinity of FcγRI/CD64, the sole “high-affinity” FcγR. CD16a N-glycan composition accounted for increases in binding affinity for the other IgG1 Fc glycoforms tested (10–50-fold). This remarkable sensitivity could only be eliminated by preventing glycosylation at Asn162 with an Asn-to-Gln mutation; mutations at the four other N-glycosylation sites preserved tighter binding in the Man5 glycoform. None of the other low-affinity FcγRs showed more than a 3.1-fold increase upon modifying the receptor N-glycan composition, including CD16b, which differs from CD16a by only four amino acid residues. This result indicates that CD16a is unique among the low-affinity FcγRs, and modifying only the glycan composition of both the IgG1 Fc ligand and receptor provides a 400-fold range in affinities.

Comments

This research was originally published in the Journal of Biological Chemistry. Subedi, Ganesh P., and Adam W. Barb. "CD16a with oligomannose-type N-glycans is the only “low-affinity” Fc γ receptor that binds the IgG crystallizable fragment with high affinity in vitro." Journal of Biological Chemistry 293, no. 43 (2018): 16842-16850. © the Author(s). doi: 10.1074/jbc.RA118.004998.

Copyright Owner

Subedi and Barb

Language

en

File Format

application/pdf

Available for download on Saturday, October 26, 2019

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