A REGION ON THE HUMAN THYROTROPIN RECEPTOR WHICH CAN INDUCE ANTIBODIES THAT INHIBIT THYROTROPIN-MEDIATED ACTIVATION OF IN-VITRO THYROID-CELL FUNCTION ALSO CONTAINS A HIGHLY IMMUNOGENIC EPITOPE

Autoantibodies to the thyrotropin receptor (TSHr) bind to the extracel lular domain of the TSHr (ETSHr) and either stimulate or inhibit thyro id cell function and/or growth. In order to investigate the regulation and the specificity of the immune response to the TSHr, our laborator y recently produced recombinant human ETSHr protein by using the bacul ovirus expression system. In the present study, we used the recombinan t ETSHr protein, a panel of overlapping synthetic peptides derived fro m the TSHr, and polyclonal rabbit antibodies produced against recombin ant ETSHr and synthetic peptides to define a highly immunogenic region (aa 352-388) of the TSHr. Moreover, we used competitive inhibition st udies to identify a dominant epitope (aa 367-372) within this region t o which ETSHr antibodies react. This immunodominant epitope lies withi n a region unique to the TSHr when compared to the other glycoprotein hormone receptors. These data, together with the earlier observation t hat antibodies against aa region 357-372 can inhibit thyrotropin (TSH) -mediated activation of thyroid cells in culture, show that aa 367-372 represents, an immunodominant epitope within a functionally important region which is unique to the TSHr. Therefore, this region may play a n important role in the induction or modulation of the specific immune response against the TSHr.