Molecular & Cellular Proteomics · 2017 · 77 citations · 48 references
Life SciencesBiochemistryImmunologyGlycobiologyImmunotherapyMolecular ImmunologyAntibody CharacterizationAntibody FunctionAntibody StructureGlycan AnalysisGlycan StructureGlycan-protein InteractionsAntibodiesAntibody GlycoformsAntibody Glycosylation EffectsFc ReceptorsFc Region StructureGlycan Recognition By AntibodiesGlycan-mediated Immune RecognitionImmunoglobulin Glycosylation
were compared with the glycan profiles of the receptors expressed in NS0 and HEK293 cells and we show that the glycan type and abundance differs significantly between the receptors and that these glycan differences lead to the observed differences in the respective FcγR binding patterns with rituximab. Oligomannose structures are prevalent on FcγRI from each source and likely contribute to the high affinity rituximab interaction through a stabilization effect. On FcγRI and FcγRIIIa large and sialylated glycans have a negative impact on rituximab binding, likely through destabilization of the interaction. In conclusion, the data show that the IgG1-FcγR binding kinetics differ depending on the glycosylation of the FcγR and further support a stabilizing role of FcγR glycans in the antibody binding interaction.
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