New revelations in susceptibility to autoimmune thyroiditis by the use of H2 and HLA class II transgenic models

Y. C.M. Kong, C. S. David

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

H2 and HLA transgenes were utilized to clarify the role of class II genes in susceptibility to experimental autoimmune thyroiditis (EAT), a model for Hashimoto's thyroiditis (HT). Susceptibility was transferred by H2 class II transgenes to a resistant haplotype and by HLA-DRA/DRBI*0301 (DR3) transgene into class II-negative Ab0 mice. Mice with a HLA-DRBI*1502 (DR2) transgene remain resistant to mouse thyroglobulin (mTg)-induced EAT, illustrating the role of HLA-DRB1 polymorphism. A role for HLA-DQ polymorphism was shown with hTg-induced EAT in HLA-DQ*0301/DQBI*0302 (DQS), but not HLA-DQ*0103/DQBI*0601 (DQ6), transgenic mice. Yet, both DQ8+ and DQ6+ mice were unresponsive to mTg. Single transgenes obviate the problems from DR/DQ linkage disequilibrium and may distinguish the degree of susceptibility and the response to shared or specific epitopes. The introduction of conserved Edk transgene into Ab0 mice reveals a new role for H2E molecules in EAT. Without H2A molecules, EαEβb molecules and T cells respond to hTg or pTg with severe thyroiditis, but not to mTg, thus distinguishing self from nonself. However, IAb genes in resistant mice ameliorate Eak transgene-mediated thyroiditis, similar to the effect of Edk transgene on IAs-mediated EAT. Studies in HLA DQ/DR double transgenic mice simulating human haplotypes could reveal HLA class II gene interactions in HT.

Original languageEnglish (US)
Pages (from-to)573-585
Number of pages13
JournalInternational Reviews of Immunology
Volume19
Issue number6
DOIs
StatePublished - Jan 1 2000

Keywords

  • Autoimmune thyroiditis
  • Autoimmunity
  • Class II gene control
  • Class II genes
  • EAT
  • H2 transgenes
  • HLA transgenes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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