Secretory IgA N- and O-glycans provide a link between the innate and adaptive immune systems

J Biol Chem. 2003 May 30;278(22):20140-53. doi: 10.1074/jbc.M301436200. Epub 2003 Mar 10.

Abstract

Secretory IgA (SIgA) is a multi-polypeptide complex consisting of a secretory component (SC) covalently attached to dimeric IgA containing one joining (J) chain. We present the analysis of both the N- and O-glycans on the individual peptides from this complex. Based on these data, we have constructed a molecular model of SIgA1 with all its glycans, in which the Fab arms form a T shape and the SC is wrapped around the heavy chains. The O-glycan regions on the heavy (H) chains and the SC N-glycans have adhesin-binding glycan epitopes including galactose-linked beta1-4 and beta1-3 to GlcNAc, fucose-linked alpha1-3 and alpha1-4 to GlcNAc and alpha1-2 to galactose, and alpha2-3 and alpha2-6-linked sialic acids. These glycan epitopes provide SIgA with further bacteria-binding sites in addition to the four Fab-binding sites, thus enabling SIgA to participate in both innate and adaptive immunity. We also show that the N-glycans on the H chains of both SIgA1 and SIgA2 present terminal GlcNAc and mannose residues that are normally masked by SC, but that can be unmasked and recognized by mannose-binding lectin, by disrupting the SC-H chain noncovalent interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid
  • Glycosylation
  • Humans
  • Immune System / metabolism*
  • Immunoglobulin A, Secretory / chemistry
  • Immunoglobulin A, Secretory / metabolism*
  • Polysaccharides / metabolism*
  • Protein Binding

Substances

  • Immunoglobulin A, Secretory
  • Polysaccharides