HLA and H2 class II transgenic mouse models to study susceptibility and protection in autoimmune thyroid disease

Yi Chi M. Kong, Jeffrey C. Flynn, Qiang Wan, Chella S. David

Research output: Contribution to journalReview article

20 Scopus citations

Abstract

Using single H2 and HLA class II transgenic mice, in the absence of endogenous H2 class II molecules, we have studied the permissiveness of class II molecules for experimental autoimmune thyroiditis (EAT). Resistant strains expressing susceptible class II molecules, H2Ak or HLA-DR3, developed EAT, clearly demonstrating the importance of class II gene inheritance. Polymorphism for HLA-DRB1 was observed, as DR3, but not DR2 or DR4, molecules were permissive for EAT induction with either mouse (m) or human (h) thyroglobulin (Tg). HLA-DQ polymorphism was also detectable, as hTg-induced EAT developed in ·DQ8+, but not DQ6+, mice. Class II gene interactions leading to reduced EAT severity were observed in H2 transgenic mice, when H2E transgene was expressed in H2A+ mice or H2A molecules were introduced into our novel H2A-E+ transgenic model. Similarly, in DR3+ mice, only the DQ8 transgene reduced EAT severity, depending on both background genes (C57BL/10 or NOD) and Tg species. Based on computer-predicted, class II-binding motifs, potential pathogenic Tg peptides, either unique to hTg (H2A-E+ model) or shared between mTg and hTg (HLA-DR3+ model), were identified. We have also developed a Graves' disease model by immunizing DR3+ mice with TSH receptor DNA. Thus, transgenic models are excellent tools to study human autoimmune thyroid diseases in the context of murine EAT.

Original languageEnglish (US)
Pages (from-to)397-404
Number of pages8
JournalAutoimmunity
Volume36
Issue number6-7
DOIs
StatePublished - Sep 1 2003

Keywords

  • Autoimmune thyroiditis
  • Autoimmunity
  • Class II interactions
  • Graves' disease model
  • H2 transgenes
  • HLA transgenes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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