title: O-methylated glycans from Toxocara are specific targets for antibody binding in human and animal infections.
abstract: The parasitic helminth Toxocara canis is a widely distributed nematode of mammals. Larval parasites, which infect a wide range of hosts including mice and humans, export glycosylated macromolecules bearing novel methylated oligosaccharide structures, similar to the mammalian blood group antigen H but bearing one or two O-methylated substitutions on the terminal fucose and subterminal galactose residues. We have studied the reactivity of synthetic forms of these glycans to parasite-specific antibodies and mammalian immune system lectins. Murine antibodies, generated to T. canis infection, predominantly recognise the mono-O-methylated form with the beta-configuration of the GalNAc residue (MoMbeta), and antibodies are entirely IgM isotype. The mAb Tcn-2 reproduces this pattern, and shows little reactivity to either the alpha isomer (MoMalpha) or the di-O-methylated form (DiM). Antibodies generated to helminth infections other than T. canis were unreactive with the glycans, except antibodies to other members of the Toxocara genus. Hence, the carbohydrate structures represent immunogenic, genus-specific antigens. Antibodies from human toxocariasis patients are reactive with the same sugars, although preferentially towards DiM. Sera from unrelated helminth infections do not react, confirming the status of these structures as Toxocara-specific glycans. The human dendritic cell lectin, DC-SIGN, was found to bind both Toxocara excretory/secretory products and mammalian blood group antigen H3. However, DC-SIGN did not bind the synthetic glycans, indicating additional non-methylated carbohydrates may also play a role in the interaction between T. canis and its host.
authors.affiliation: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh EH9 3JT, UK.
authors.forename: Irma
authors.initials: I
authors.lastname: Schabussova
authors.forename: Hassan
authors.initials: H
authors.lastname: Amer
authors.forename: Irma
authors.initials: I
authors.lastname: van Die
authors.forename: Paul
authors.initials: P
authors.lastname: Kosma
authors.forename: Rick M
authors.initials: RM
authors.lastname: Maizels
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000276:immunology; D005260:Female; D006373:Helminthiasis / Q000276:immunology; D006358:Hot Temperature; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D037102:Lectins / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D009844:Oligosaccharides / Q000276:immunology; D011134:Polysaccharides / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology; D017166:Toxocara canis / Q000276:immunology*; D014120:Toxocariasis / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000909:Antibodies, Helminth; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D000939:Epitopes; D007075:Immunoglobulin M; D037102:Lectins; D037181:Lectins, C-Type; D009844:Oligosaccharides; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin