DISTINCT GENETIC PATTERN OF MOUSE SUSCEPTIBILITY TO THYROIDITIS INDUCED BY A NOVEL THYROGLOBULIN PEPTIDE

Experimental autoimmune thyroiditis (EAT), induced by thyroglobulin (T g) and adjuvant, is major histocompatibility complex-controlled and de pendent on Tg-reactive T cells, but the immunopathogenic T-cell epitop es on Tg remain mostly undefined. We report here the thyroiditogenicit y of a novel rat Tg peptide (TgP2; corresponding to human Tg amino aci ds 2695-2713), identified by algorithms as a site of putative T-cell e pitope(s). TgP2 causes EAT in SJL (H-2(s)) but not in C3H or B10.BR (H -2(k)), BALB/c (H-2(d)), and B10 (H-2(b)) mice. This reveals a new gen etic pattern of EAT susceptibility, since H-2(k) mice are known to be high reponders (susceptible) after Tg challenge. Following in vivo pri ming with TgP2, T cells from only SJL mice proliferated significantly and consistently to TgP2 in vitro, whereas TgP2-specific IgG was obser ved in all strains tested. Adoptive transfer of TgP2- primed SJL lymph node cells to naive syngeneic recipients induced a pronounced mononuc lear infiltration of the thyroid, which was more extensive than that o bserved after direct peptide challenge. TgP2 is nonimmunodominant, sin ce priming of SJL mice with rTg did not consistently elicit T-cell res ponses to TgP2 in vitro and a TgP2-specific T-cell hybridoma did not r espond to antigen presenting cells pulsed with rTg. The data support t he notion that Tg epitopes need not be either iodinated or immunodomin ant in order to cause severe thyroiditis and that the genetic pattern of the disease they induce can be distinct from that of Tg-mediated EA T.