Human thyroglobulin peptide p2340 induces autoimmune thyroiditis in HLA-DR3 transgenic mice

Evangelos Karras, Huan Yang, Peggy Lymberi, Premkumar Christadoss

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

In a previous study we demonstrated that the human thyroglobulin (hTg) peptide p2340 (aa 2340-2359) can stimulate a T cell response and elicit experimental autoimmune thyroiditis (EAT) in AKR/J (H-2k) mice. In the present study we examined whether p2340 can induce EAT in single HLA class II DR3 transgenic mice. This peptide was found to be immunogenic at the T cell level in DR3 mice, since it induced specific proliferative responses, as well as IL-2 and IFN-γ secretion in secondary cultures of peptide-primed lymph node cells (LNC). Immunization of HLA-DR3 mice with p2340 in CFA elicited EAT (infiltration index of 1 to 2) in eight of nine mice. Peptide-primed LNC responded to intact hTg, whereas, hTg-primed LNC did not respond to p2340 in culture, suggesting that p2340 contains subdominant T cell epitope(s). P2340 was also found to be immunogenic at the B cell level, since strong p2340-specific IgG response was detected in all transgenic mice tested. Thus, we provide evidence for a pathogenic role of an hTg peptide in HLA-DR3 transgenic mice. Therefore, p2340 could be presented by DR3 molecule in patients with Hashimoto's thyroiditis and participate in the development of the disease.

Original languageEnglish (US)
Pages (from-to)291-296
Number of pages6
JournalJournal of Autoimmunity
Volume24
Issue number4
DOIs
StatePublished - Jun 1 2005

Keywords

  • Experimental autoimmune thyroiditis
  • HLA-DR3 transgenic mice
  • T cell epitope
  • Thyroglobulin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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