Induction of autoimmune thyroiditis by unique human thyroglobulin epitopes in H2E transgenic mice

Q. Wan, D. J. McCormick, R. Shah, A. A. Giraldo, C. S. David, Y. M. Kong

Research output: Contribution to journalArticle

Abstract

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 languageEnglish (US)
Pages (from-to)A1051
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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