Human autoantibodies to thyroglobulin are directed towards a restricted number of human specific epitopes.
Significant binding of thyroglobulin (Tg) autoantibodies was restricted to primate Tg, although some sera showed weak cross-reactivities with other species at high concentrations. In contrast rabbit anti-human Tg bound to all other animals' Tg in addition to human and this was not due to crossreactions with the thyroxyl residues. Mouse antihuman Tg monoclonal antibodies (MoAb) showed at least three different patterns of cross-reactivities. Group 1 MoAb, like Tg autoantibodies, were primate specific; two out of six MoAb bound only human Tg. Group 2 MoAb also bound a few other animals' Tg in addition to human. Of the three MoAb in group 3, two reacted with most or all of eight animal Tg tested while the other bound to all eight. However the binding of thirteen out of the fourteen MoAb against human Tg including all of the primate Tg specific group 1 MoAb was not inhibited by any of the nine Tg autoantibodies. Reactions of MoAb with heat-treated human Tg varied. Examples of decreased, increased or no change in reactivity could be demonstrated. On this basis at least five or possibly six separate human-specific epitopes could be defined by group 1 MoAb. Monoclonal antibody 1D6 (group 2) was inhibited by six out of nine Tg autoantibodies at high concentrations. This MoAb, similarly to the eight Tg autosera tested, had reduced reactivity with heat treated Tg. These studies demonstrated that human Tg has immunogenic structures conserved in the Tg of many species. The protein also has, however, primate and human-specific antigenic sites but at least five or possibly six of these are not related to autoantibody binding.
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D001667:Binding, Competitive; D002417:Cattle; D002645:Chickens; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology*; D006111:Graves Disease / Q000276:immunology*; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010215:Papio; D011817:Rabbits; D012756:Sheep; D013045:Species Specificity; D013552:Swine; D013954:Thyroglobulin / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D013954:Thyroglobulin