title: Secretory IgA N- and O-glycans provide a link between the innate and adaptive immune systems.
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.
authors.affiliation: Glycobiology Institute, Department of Biochemistry, Oxford University, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Royle
authors.forename: Anja
authors.initials: A
authors.lastname: Roos
authors.forename: David J
authors.initials: DJ
authors.lastname: Harvey
authors.forename: Mark R
authors.initials: MR
authors.lastname: Wormald
authors.forename: Daniëlle
authors.initials: D
authors.lastname: van Gijlswijk-Janssen
authors.forename: El-Rashdy M
authors.initials: el-RM
authors.lastname: Redwan
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Dwek
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
mesh_terms: 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
chemical_list: D007071:Immunoglobulin A, Secretory; D011134:Polysaccharides