Terminal sugars of Fc glycans influence antibody effector functions of IgGs

Curr Opin Immunol. 2008 Aug;20(4):471-8. doi: 10.1016/j.coi.2008.06.007. Epub 2008 Jul 17.

Abstract

IgG molecules contain glycans in the CH2 domain of the Fc fragment (N-glycosylation) which are highly heterogeneous, because of the presence of different terminal sugars. The heterogeneity of Fc glycans varies with species and expression system. Fc glycans influence the binding of IgG to Fc receptors and C1q, and are therefore important for IgG effector functions. Specifically, terminal sugars such as sialic acids, core fucose, bisecting N-acetylglucosamine, and mannose residues affect the binding of IgG to the FcgammaRIIIa receptor and thereby influence ADCC activity. By contrast, terminal galactose residues affect antibody binding to C1q and thereby modulate CDC activity. Structural studies indicate that the presence or absence of specific terminal sugars may affect hydrophilic and hydrophobic interactions between sugar residues and amino acid residues in the Fc fragment, which in turn may impact antibody effector functions.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibody-Dependent Cell Cytotoxicity*
  • Humans
  • Immunoglobulin Fc Fragments / chemistry
  • Immunoglobulin Fc Fragments / immunology*
  • Immunoglobulin Fc Fragments / metabolism
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / metabolism
  • Polysaccharides / chemistry
  • Polysaccharides / immunology*
  • Polysaccharides / metabolism

Substances

  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Polysaccharides