AUTOREACTIVE IGG ELICITED IN MICE BY THE NONDOMINANT BUT PATHOGENIC THYROGLOBULIN PEPTIDE-(2495-2511) - IMPLICATIONS FOR THYROID AUTOIMMUNITY

We have previously shown that mice challenged with the rat thyroglobul in (Tg) peptide TgP1 (corresponding to aa 2495-2511 of human Tg) devel op experimental autoimmune thyroiditis (EAT) and produce IgG antibodie s that cross-react with Tg from various species. It was not clear, how ever, whether such antibodies were TgP1-specific or were induced secon darily-i.e. by autologous Tg released from the destroyed gland-and the refore directed to determinants other than TgP1. In this study we desc ribe that, 5 weeks after priming with TgP1, the binding of serum IgG o n native Tg is completely inhibited by free peptide, suggesting lack o f recognition of other determinants on mouse Tg (mTg). In addition, Tg P1-induced but not mTg-induced IgG bound better to heat-denatured than intact mTg, a result compatible with the recognition of a linear epit ope by the peptide-induced antibodies. Comparison of the IgG subclass distribution among mTg-induced versus TgP1-induced IgG did not reveal qualitative differences, since all subclasses were represented in the order IgG1 > IgG2b > IgG2a > IgG3. Finally, TgP1-specific IgG reacted strongly with the follicular colloid in sections of normal thyroids, i ndicating the potential to bind to native Tg in vivo. These data: (i) highlight TgP1 as the only, so far, Tg sequence known to generate both EAT and Tg-reactive IgG in mice; and (ii) do not provide evidence for an amplification of the Tg-specific IgG response through the involvem ent of endogenous autoantigen in EAT.