NOVEL TYVELOSE-CONTAINING TRI-ANTENNARY AND TETRA-ANTENNARY N-GLYCANSIN THE IMMUNODOMINANT ANTIGENS OF THE INTRACELLULAR PARASITE TRICHINELLA-SPIRALIS

The larval stage of the intestinal nematode, Trichinella spiralis, sec retes and displays on its cuticle a number of antigenically cross-reac tive glycoproteins. These so-called TSL-1 antigens induce a powerful a ntibody response in parasitized animals. In rats, anti-TSL-1 antibodie s mediate a protective immunity that expels invading larvae from the i ntestine. The vast majority of anti-TSL-1 antibodies are specific for glycans. Although the biological functions of TSL-1 antigens are not k nown, the powerful effect of glycan-specific antibodies on the intesti nal survival of T.spiralis suggests that they play an important role i n parasite establishment. Little is known about the structures of the glycans present on the TSL-1 glycoproteins. Recent studies have sugges ted, however, that the antigens contain very unusual glycans (Wisnewsk i,N., McNeil,M., Grieve,R.B. and Wassom,D.L., Mol. Biochem. Parasitol, 61, 25-36, 1993). Sugar and linkage analysis of the combined secreted products unexpectedly showed that a major terminal sugar is tyvelose (3,6-dideoxy-D-arabinohexose; Tyv) which has previously been found onl y in certain gram-negative bacterial lipopolysaccharides. In this pape r, we report the first rigorous structural study of oligosaccharides r eleased from TSL-1 antigens by peptide N-glycosidase F digestion. Usin g strategies based on fast atom bombardment mass spectrometry (FAB-MS) , we have discovered a novel family of tri- and tetra-antennary N-glyc ans whose antennae are comprised of the tyvelose-capped structure: Tyv 1,3GalNAc beta 1,4(Fuc alpha 1,3) GlcNAc beta 1-. Thus a major populat ion of TSL-1 glycans contains clusters of hydrophobic terminal structu res which are likely to be highly immunogenic.