Flexibility of TCR repertoire and permissiveness of HLA-DR3 molecules in experimental autoimmune thyroiditis in nonobese diabetic mice

Jeffrey C. Flynn, Brian E. Fuller, Alvaro A. Giraldo, John C. Panos, Chella S. David, Yi Chi M Kong

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Experimental autoimmune thyroiditis (EAT) is inducible in genetially susceptible mice by immunization with mouse thyroglobulin (mTg). With susceptibility linked to MHC class II, EAT is useful in studying human leukocyte antigen (HLA) associations with Hashimoto's thyroiditis. In non-obese diabetic (NOD) mice, ∼10% thyroiditis incidence occurs with aging. This potential was exploited to examine the T cell repertoire and HLA association in EAT. Similar to B10.K-Vβc mice with TCRBV genes reduced by ∼70%, mTg-immunized NOD-Vβc mice developed thyroiditis comparable to controls, indicating plasticity of the TCR repertoire for 'pathogenic epitopes. HLA association was evaluated by introducing HLA-DRA/DRB1*0301 (DR3) transgene into class II-negative NOD mice (Ab0/NOD). Previously, this HLA-DR3 transgene rendered EAT-resistant B10.M and Ab0 mice susceptible to both mTg- and hTg-induced EAT. These results are now confirmed, mTg-induced thyroiditis in DR3+ Ab0/NOD mice was comparable to that in NOD and DR3- NOD mice, and the proliferative response was stronger. By comparison, NOD mice were only moderately susceptible to hTg-induced EAT. However, thyroiditis was more severe in DR3+ Ab0/NOD than in DR3- NOD mice, with no difference in proliferative response to hTg harbouring heterologous epitopes. The confirmed permissiveness of HLA-DR3 molecules on an NOD background for EAT induction by both mTg and hTg supports the importance of this class II gene implicated in some patient studies.

Original languageEnglish (US)
Pages (from-to)7-15
Number of pages9
JournalJournal of Autoimmunity
Volume17
Issue number1
DOIs
StatePublished - Aug 1 2001

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Keywords

  • Autoimmune thyroiditis
  • EAT
  • HLA-DR3
  • NOD
  • TCRBV

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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