Secretory IgA N- and O-glycans provide a link between the innate and adaptive immune systems.
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.
Royle
Louise
L
Glycobiology Institute, Department of Biochemistry, Oxford University, United Kingdom.
Roos
Anja
A
Harvey
David J
DJ
Wormald
Mark R
MR
van Gijlswijk-Janssen
Daniëlle
D
Redwan
El-Rashdy M
el-RM
Wilson
Ian A
IA
Daha
Mohamed R
MR
Dwek
Raymond A
RA
Rudd
Pauline M
PM
D002851:Chromatography, High Pressure Liquid; D006031:Glycosylation; D006801:Humans; D007107:Immune System / Q000378:metabolism*; D007071:Immunoglobulin A, Secretory / Q000737:chemistry / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding
D007071:Immunoglobulin A, Secretory; D011134:Polysaccharides