Induction of experimental autoimmune thyroiditis in rats with the synthetic peptide (2495-2511) of thyroglobulin

We have previously shown that the synthetic 17 mer peptide TgP1 (a.a. 2495-2511) from the rat thyroglobulin (Tg) sequence is thyroiditogenic in mice and consists of nonimmunodominant but highly immunogenic determinants at the T or B cell level. Although TgP1 appears to be phylogenetically conserved, it remains uncertain whether it is a self-peptide in mice since the mouse Tg amino acid sequence is unknown. In this report, we demonstrate that TgP1 also induces experimental autoimmune thyroiditis (EAT) in WKY, F344, and WF strains of rats that are known to be EAT-susceptible after Tg challenge. Priming of all strains with TgP1 led to strong proliferative lymph node cell responses to the peptide in vitro that were abrogated by MAbs against CD4, OX-6, and OX-17 determinants, suggesting TgP1 recognition by class II-restricted T cells. In vivo priming with autologous or heterologous Tg did not lead to TgP1-specific proliferation in vitro confirming the cryptic nature of this sequence in rats. In contrast to findings in the mouse, strong peptide-specific IgG responses were not observed in rats despite the presence of EAT. These data demonstrate that TgP1 is immunopathogenic in an autologous system and provide the first evidence of a defined autoantigenic Tg peptide in rats.