T and B epitope determination and analysis of multiple antigenic peptides for the Schistosoma mansoni experimental vaccine triose-phosphate isomerase.
Schistosoma mansoni triose-phosphate isomerase (TPI), a glycolytic enzyme, was originally identified as the target of the mAb M.1 that conferred protection when the antibody was administered in vivo. In this study we increase the evidence that schistosome TPI is a potential vaccine Ag by showing that it also a potent inducer of IL-2 and IFN-gamma production (Th1 responses), driving production of these cytokines in the same cell populations of infected animals that have high Th2 responses directed at other parasite egg Ag. With the goal of synthetic peptide vaccine design, rTPI was used to determine specific T and B cell epitopes recognized by two strains of mice representing high and moderate responders (C57Bl/6J and CBA/J). All selected epitopes were from nonconserved regions of TPI and thus parasite-specific. We then defined minimal size immunoreactive epitopes and synthesized four-armed multiple antigenic peptides (MAP) consisting of T and B cell epitopes that could be recognized by both strains of mice in the same molecule. Characterization of the immunoreactivity of the MAP showed that higher antibody recognition of the MAP was attained when the B cell epitope was placed on the amino termini relative to the T cell epitope, whereas equivalent immunoreactivity occurred for the T cell epitopes when located at either position. Most interesting was the finding that one of the minimal T cell epitopes, when incorporated into the MAP, required enlarging to retain immunoreactivity. Finally we showed that both the full-length TPI molecule and the final version of the MAP were immunogenic to T cells in naive animals and induced cross-recognition in the form of IL-2 and IFN-gamma production.
Reynolds
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SR
Department of Tropical Public Health, Harvard School of Public Health, Boston, MA 02115.
Dahl
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CE
Harn
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D000595:Amino Acid Sequence; D000818:Animals; D000947:Antigens, Helminth / Q000737:chemistry* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000032:analysis; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012550:Schistosoma mansoni / Q000201:enzymology / Q000276:immunology*; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D014305:Triose-Phosphate Isomerase / Q000737:chemistry / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000276:immunology
D000947:Antigens, Helminth; D000939:Epitopes; D010455:Peptides; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014305:Triose-Phosphate Isomerase