Brusić, Vladimir

Abstract Experimental autoimmune thyroiditis (EAT) is a model for Hashimoto’s thyroiditis which is characterized by mononuclear cell infiltration and follicular destruction. We previously reported on an Eα-transgenic strain (H2A−E+) that is highly susceptible to human (h) thyroglobulin (Tg)-induced EAT, but strongly tolerant to mouse (m)Tg. After mTg and adjuvant, traditional, resistant strains do not develop thyroiditis, nor detectable primed T cell proliferation, but do make anti-mTg Abs. By contrast, this H2Eb+ strain does not even produce mTg Abs. To identify what epitopes in the mouse thyroid hTg-primed, thyroiditogenic T cells recognize to evoke EAT, we first confirmed that hTg-primed cells do not respond to mTg, nor to other thyroid Ags. We next selected the three immunogenic epitopes on hTg known to be processed and presented by H2Eb, as the basis for synthesizing potential mTg epitopes. One 15-mer peptide, mTg409, did prime T cells, elicit Ab, and generate moderate thyroiditis. Thyroiditis incidence was increased after adoptive transfer of in vitro activated, mTg409-primed cells. Moreover, cells primed to hTg410, the corresponding, pathogenic hTg peptide, cross-reacted with mTg409, and vice versa. This mTg autoepitope, identified by using thyroiditogenic hTg epitopes, helps to explain the severe thyroiditis seen in this novel H2E+ transgenic model. (Supported by NIH grant DK45960)