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

The Journal of Biological Chemistry
Ganesh P Subedi, Adam W Barb

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 incre...Continue Reading

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Citations

Jan 1, 2020·Molecular & Cellular Proteomics : MCP·Jacob T RobertsAdam W Barb
Mar 7, 2019·Frontiers in Immunology·Kashyap R PatelAdam W Barb
Nov 12, 2020·The Journal of Biological Chemistry·Adam W Barb
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Jacob T RobertsAdam W Barb
Mar 5, 2021·The Journal of Physical Chemistry. B·Carl A Fogarty, Elisa Fadda
Mar 31, 2020·Molecular Immunology·Florian CambayGregory De Crescenzo
Jan 8, 2021·The Journal of Biological Chemistry·Adam W Barb
Jul 3, 2021·International Journal of Molecular Sciences·Catherine Forest-NaultGregory De Crescenzo

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