Evaluation of T cell stimulation by thyrotropin-receptor epitopes in Graves' disease

In Graves' disease (GD) immunized T cells reactive to TSH-receptor epitopes contribute to pathogenesis through B cell help, and cytotoxicity. We evaluated T cell responses to synthetic TSH-receptor epitopes in hyperthyroid patients with GD prior to therapy, at 6-8 weeks after radioactive iodine (RAI) administration, or 6-8 months later when euthyroid, and in control subjects. All T cell responses were relatively low as generally found in human autoimmune diseases. Responses in hyperthyroid GD patients were significantly greater than among controls, were augmented 6-8 weeks after RAI treatment, were still present after patients became euthyroid, and did not differ between DR3+ and non-DR3+ patients. Patient's T cells reacted to multiple different epitopes, and reactivity differed depending on the course of the disease and treatment.While certain epitopes most commonly cause T cell reactivity, we did not find evidence for a single or few "dominant" epitopes.