Experimental autoimmune thyroiditis (EAT), a model for Hashimoto's thyroiditis, can be induced by injecting either mouse (M) or human (H) thyroglobulin (Tg) into genetically susceptible mice. EAT susceptibility is linked to H2A class II genes; k & s haplotypes are susceptible, while b & f are resistant. The introduction of H2A k or HLA-DRB1 *0301 (DR3) transgene into resistant B10.M (H2 f) or class II knock-out Ab 0 mice led to severe thyroid infiltration. These transgenic strains responded to EAT induction with both MTg and HTg. Here, we introduced H2Ea transgene into resistant B10 (H2 b) or Ab 0 mice, resulting in surface Eβ b expression. To our surprise, both transgenic strains showed severe inflammation only after HTg, but not MTg, immunization. In proliferative assays, HTg-primed cells did not respond to MTg, and stimulation with HTg was blocked by anti-Eβ b. We also tested three primary hormonogenic site 12mer peptides, 100% identical between MTg and HTg. Although two can activate T cells for thyroiditis transfer and cytotoxicity, none stimulated HTg-primed cells. Previous cross-activation and cross-tolerance studies with MTg and HTg suggested that MTg had both conserved and unique T cell epitopes. This is the first demonstration of HTg-unique epitopes.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology