T cell responses to synthetic TSH receptor peptides in Graves' disease

Twenty-eight peptides, representing the entire extracellular domain of the TSH receptor, were synthesised to investigate which parts of this autoantigen may be targets for the T cell response in Graves' disease (GD). T cells from 11 of 21 controls and 26 of 36 newly diagnosed GD patients proliferated in response to one or more peptides with a stimulation index (SI) of greater than 2.0 (chi 2 = 2.31, P greater than 0.1). The response of patients and controls to any of the individual peptides was also not statistically different. However, individual patients gave high SIs with certain peptides to which controls either gave an absent or very weak response. HLA-DR3 was not associated with any particular response to TSHR peptides. Three out of seven GD patients whose T cells were evaluated before and after treatment showed a response of this kind only early in the course of their disease. Intrathyroidal T cells from four GD patients did not give a consistent proliferative response to pools of five peptides, and depleting peripheral blood T cells of their CD8+ population did not affect the proliferative response. These results indicate that the T cell response to the TSH receptor in GD does not seem to be directed against any one particular epitope on the peptides we have tested which cover the extracellular domain.