HLA-DR and HLA-DQ polymorphism in human thyroglobulin-induced autoimmune thyroiditis: DR3 and DQ8 transgenic mice are susceptible

Qiang Wan, Rajal Shah, John C. Panos, Alvaro A. Giraldo, Chella S. David, Yi Chi M. Kong

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

In contrast to H2-based susceptibility to experimental autoimmune thyroiditis (EAT) induced with thyroglobulin (Tg), human leukocyte antigen (HLA) association with Hashimoto's thyroiditis, the human counterpart, is less clear, and determining association is further complicated by DR/DQ linkage disequilibrium. Previously, we addressed the controversial implication of HLA-DR genes by introducing HLA-DRA/DRB1*0301 (DR3) transgene into endogenous class II negative H2Ab0 mice. EAT induction with either human (h) or mouse (m) Tg demonstrated the permissiveness of DR3 molecules for shared Tg epitopes. Here, we examined the participation of HLA-DQ genes by introducing DQA1*0301/DQB1*0302 (DQ8) transgene into class II negative Ab0 or class I and II negative β2m(-/-) Ab0 mice. About 50% and 80% of HLA-DQ8+ Ab0 and β2m- Ab0 mice, respectively, developed moderate EAT after hTg immunization, but only minimal response to mTg. The hTg presentation to hTg-primed cells was blocked by anti-DQ mAb in vitro. By contrast, HLA-DRB1*1502 (DR2) and *0401 (DR4) transgenes contributed little to hTg induction. Similarly, DQA1*0103/DQB1*0601 or DQA1*0103/DQB1*0602 (DQ6) transgenic Ab0 mice were unresponsive to hTg induction and carried no detectable influence in DQ8/DQ6 double transgenic mice. Thus, both HLA-DR and -DQ polymorphism exists for hTg in autoimmune thyroiditis. The use of defined single or double transgenic mice obviates the complications seen in polygenic human studies.

Original languageEnglish (US)
Pages (from-to)301-310
Number of pages10
JournalHuman Immunology
Volume63
Issue number4
DOIs
StatePublished - Apr 23 2002

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Keywords

  • EAT
  • EAT in HLA transgenic mice
  • Experimental autoimmune thyroiditis
  • HLA polymorphism in EAT
  • hTg in HLA transgenic mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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