Antigenic determinants on thyroglobulin: comparison of the reactivities of different thyroglobulin preparations with serum antibodies and T cells of patients with chronic thyroiditis.
To delineate the antigenic determinants on thyroglobulin (Tg) recognized by serum autoantibodies and peripheral blood T cells from patients with chronic thyroiditis, we studied the reactivities of three different Tg preparations, i.e. enzyme-digested Tg fragments, physically or chemically denatured Tg, or Tg with differing iodine contents. Human Tg was digested with staphylococcal V8 protease, and the fragments were separated by high performance liquid chromatography. The autoantibodies reacted with the larger fragments, but their ability to bind to small fragments was limited. On the other hand, T cells reacted similarly with all fragments, regardless of mol wt. The autoantibodies bound little to denatured Tg after its disulfide bonds were destroyed with dithiothreitol or 2-mercaptoethanol, while the reactivity of heat-denatured Tg was partially decreased, and that of Tg denatured with sodium dodecyl sulfate was conserved. Conversely, T cells reacted with Tg denatured by heating or dithiothreitol treatment. These results indicate that autoantibodies recognize mainly a conformational structure of Tg, presumably containing disulfide bonds, whereas T cells recognize the primary structure of Tg. Variations in the iodine content of Tg were not associated with altered reactivity with autoantibodies or T cells. We propose that variations in Tg conformation related to iodination of the molecule do not contribute significantly to its reactivity with autoantibodies and T cells. In addition, T cells reacted with the smaller Tg fragments containing few T3 or T4 residues to a greater extent than they did with larger Tg fragments with the same amount of T3 or T4 as native Tg. Therefore, it appears that the Tg-reactive T cells predominantly recognize determinants on the Tg molecule that are unrelated to hormone-containing sites.
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D002908:Chronic Disease; D000939:Epitopes / Q000032:analysis*; D005260:Female; D006801:Humans; D007455:Iodine / Q000502:physiology; D008213:Lymphocyte Activation; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology*; D013966:Thyroiditis / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D013954:Thyroglobulin; D007455:Iodine