Topologic mapping of protective and nonprotective epitopes on the variant surface glycoprotein of the WRATat 1 clone of Trypanosoma brucei rhodesiense.
Monoclonal antibodies were used in competitive antibody binding assays to define and map epitopes on the variant surface glycoprotein of the WRATat 1 clone of T. b. rhodesiense. By using a panel of 30 WRATat 1-specific monoclonal antibodies, 16 epitopes were defined that fall into four clusters, having 1, 1, 3, and 11 distinct epitopes respectively. All epitopes were easily classified as being 1) exposed uniformly on the surface of the trypanosome, 2) exposed only in the region of the flagellar pocket, or 3) "buried", based on the ability or inability of the monoclonal antibodies to bind living trypanosomes in a fluid phase immunofluorescence assay. Monoclonal antibodies that bind exposed surface epitopes are protective, whereas only three of seven that bind exclusively to flagellar pocket epitopes are protective. None of the nine monoclonal antibodies that recognize buried epitopes are protective. Also, antibody-mediated immunity to WRATat 1 trypanosomes is not associated with any particular subclass of antibody. The IgM, IgG1, IgG2a, IgG2b, IgG3, and IgA subclasses each contain examples of protective monoclonal antibodies.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000954:Antigens, Surface / Q000276:immunology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D014346:Trypanosoma brucei brucei / Q000276:immunology* / Q000378:metabolism; D014353:Trypanosomiasis, African / Q000276:immunology / Q000517:prevention & control; D014643:Variant Surface Glycoproteins, Trypanosoma
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D006023:Glycoproteins; D014643:Variant Surface Glycoproteins, Trypanosoma