A unique multifucosylated -3GalNAcβ1→4GlcNAcβ1→3Galα1- motif constitutes the repeating unit of the complex O-glycans derived from the cercarial glycocalyx of Schistosoma mansoni

Abstract

The entire surface of the cercarial stage of the human blood fluke Schistosoma mansoni is covered by a 1-μm thick, highly immunogenic, fucose-rich glycocalyx (GCX). Using strategies based on enzymatic, chemical, and mass spectrometric analysis, we have defined the structures of the major glycans released by reductive elimination from GCX. They comprise a heterogeneous population of multifucosylated complex oligosaccharides with the following nonreducing terminal sequences: ± Fucα1 →2Fucα1 →3GalNAcβ1 →4GlcNAcβ1 3Galα1 → 3+ ± Fucα1 →2Fucα1 →2Fucα1 STRUCTURE 1 Our structural data suggest that these tri- to pentafucosylated epitopes are carried on type 1, R →Ga1β1→3GalNAc, and type 2, R→Galβ1→3(R→GlcNAcβ1→6) GalNAc, core structures via repeat units of (3GalNAcβ1→4(Fucα1→2Fucα1→2Fucα1→3) GlcNAcβ1→3Galα→)n, where n is mainly 0 and 1, and all sugars are in the pyranose form. The proposed structure represents the first instance where an α-galactosylated β-GalNAc(1→4)-β-GlcNAc sequence occurs as a repeating unit in a glycoprotein. It is also unique in being substituted with oligofucosyl appendages. The unusual oligosaccharide structures described here, particularly the potentially immunodominant oligofucosyl moieties, are most likely responsible for the known potency of GCX in modulating various immune responses including complement activation, B cell mitogenesis, and delayed type hypersensitivity in schistosomiasis.