Terminal beta-linked tyvelose creates unique epitopes in Trichinella spiralis glycan antigens.
Indirect evidence that the immunodominant N-glycans of the parasite, Trichinella spiralis are capped by novel beta-linked 3,6-dideoxy-D-arabinohexopyranosyl residues (tyvelose, Tyv) was obtained from immunochemical assays employing monoclonal antibodies and synthetic oligosaccharides. Three of four previously characterized monoclonal antibodies generated from the lymphocytes of T.spiralis infected rats bind BSA glycoconjugates bearing the synthetic epitope beta-D-Tyvp(1-->3)-beta-D-GalNAcp but not to the corresponding alpha-D-Tyvp(1-->3)-beta-D-GalNAcp-BSA glycoconjugate. Monosaccharide and disaccharide glycoside inhibition data mirrors the results of the direct binding experiments. The branched tetrasaccharide beta-D-Tyv(1-->3)-beta-D-GalNAcp(1-->4)[alpha-L-Fucp(1 -->3)] beta-D-GalNAcp is the most active synthetic oligosaccharide inhibitor for all four monoclonal antibodies studied, while the corresponding alpha-D-Tyv containing tetrasaccharide and the core trisaccharide beta-D-GalNAcp(1-->4)[alpha-L-Fucp(1-->3)]beta-D-GlcNAcp+ ++ are inactive. The exceptional inhibitory activity of the disaccharide beta-D-Tyvp(1-->3)-beta-D-GalNAcp with one mAb (18H) compared to that of the branched tetrasaccharide beta-D-Tyvp(1-->3)-beta-D-GalNAcp(1-->4)[alpha-L-Fucp( 1-->3)]-beta-D-GlcNAcp is indicative of the presence of linear, nonfucosylated glycan epitopes (beta-D-Tyvp(1-->3)-beta-D-GalNAcp(1-->4) beta-D-GlcNAcp) that lack a fucose residue in one arm of the antigenic, tetra-antennary N-glycan. This observation supports earlier FAB-mass spectrometry evidence for the existence of tetra-antennary, core fucosylated glycans that lack a fucose residue on one of their antennae.
Ellis
L A
LA
James A. Baker Institute for Animal Health, Cornell University, College of Veterinary Medicine, Ithaca, NY, USA.
McVay
C S
CS
Probert
M A
MA
Zhang
J
J
Bundle
D R
DR
Appleton
J A
JA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000947:Antigens, Helminth / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D000939:Epitopes / Q000737:chemistry*; D005643:Fucose / Q000032:analysis; D006601:Hexoses / Q000737:chemistry* / Q000276:immunology*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011134:Polysaccharides / Q000276:immunology*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000276:immunology; D016339:Spectrometry, Mass, Fast Atom Bombardment; D017160:Trichinella spiralis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D000939:Epitopes; D006601:Hexoses; D011134:Polysaccharides; D012710:Serum Albumin, Bovine; D005643:Fucose; C009616:tyvelose