Autoimmune T-cell recognition sites of human thyrotropin receptor in Graves' disease

Five overlapping synthetic peptides representing two regions of thyrotropin (TSH) binding sites of human thyrotropin receptor (TSHR) (peptides 12-30, 24-44, 308-328, 324-344 and 339-364) were investigated for their ability to cause proliferation of peripheral blood lymphocytes (PBL) from eight patients with Graves' disease. The same experiment was done using PBL from four cases with Hashimoto's thyroiditis, two cases with subacute thyroiditis, two cases with rheumatoid arthritis (RA) and eight normal volunteers. PBL obtained from each patient with Graves' disease responded to one or more of peptides 12-30, 24-44, 308-328 and 324-344, while peptide 339-364 had no stimulating activity. The level of stimulating activity of each of the four aforementioned TSHR peptides varied from patient to patient. None of the five TSHR peptides caused the proliferation of PBL from patients with Hashimoto's thyroiditis, subacute thyroiditis, or RA and from normal volunteers. The results indicate that the proliferation of PBL by TSHR peptides is specific in patients with Graves' disease and that the regions of TSHR which are involved in the binding to TSH are also the target of autoimmune T-cell recognition in Graves' disease. The difference in T-cell response from patient to patient could be explained by genetic regulation toward each autodeterminant.