Novel tyvelose-containing tri- and tetra-antennary N-glycans in the immunodominant antigens of the intracellular parasite Trichinella spiralis.
The larval stage of the intestinal nematode, Trichinella spiralis, secretes and displays on its cuticle a number of antigenically cross-reactive glycoproteins. These so-called TSL-1 antigens induce a powerful antibody response in parasitized animals. In rats, anti-TSL-1 antibodies mediate a protective immunity that expels invading larvae from the intestine. The vast majority of anti-TSL-1 antibodies are specific for glycans. Although the biological functions of TSL-1 antigens are not known, the powerful effect of glycan-specific antibodies on the intestinal survival of T. spiralis suggests that they play an important role in parasite establishment. Little is known about the structures of the glycans present on the TSL-1 glycoproteins. Recent studies have suggested, however, that the antigens contain very unusual glycans (Wisnewski, 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-arabino-hexose; Tyv) which has previously been found only in certain gram-negative bacterial lipopolysaccharides. In this paper, we report the first rigorous structural study of oligosaccharides released from TSL-1 antigens by peptide N-glycosidase F digestion. Using strategies based on fast atom bombardment mass spectrometry (FAB-MS), we have discovered a novel family of tri- and tetra-antennary N-glycans whose antennae are comprised of the tyvelose-capped structure: Tyv1,3GalNAc beta 1,4(Fuc alpha 1,3)GlcNAc beta 1-. Thus a major population of TSL-1 glycans contains clusters of hydrophobic terminal structures which are likely to be highly immunogenic.
Reason
A J
AJ
Department of Biochemistry, Imperial College of Science, Technology and Medicine, South Kensington, London, UK.
Ellis
L A
LA
Appleton
J A
JA
Wisnewski
N
N
Grieve
R B
RB
McNeil
M
M
Wassom
D L
DL
Morris
H R
HR
Dell
A
A
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006026:Glycoside Hydrolases; D006601:Hexoses / Q000737:chemistry*; D006868:Hydrolysis; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000032:analysis / Q000276:immunology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism; D017160:Trichinella spiralis / Q000276:immunology*
D000947:Antigens, Helminth; D006601:Hexoses; D016056:Immunodominant Epitopes; D011134:Polysaccharides; C009616:tyvelose; D006026:Glycoside Hydrolases