Pathogenic human thyroglobulin peptides in HLA-DR3 transgenic mouse model of autoimmune thyroiditis

Jeffrey C. Flynn, Daniel J. McCormick, Vladimir Brusic, Qiang Wan, John C. Panos, Alvaro A. Giraldo, Chella S. David, Yi Chi M. Kong

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

To identify pathogenic epitopes on human thyroglobulin (hTg), a homodimer of 660 kDa, we have applied a computer-based algorithm to predict potential HLA-DR3-binding peptides and have tested them in DR3-transgenic mice. Of the 39 peptides selected, four stimulated a proliferative response from hTg-primed cells of DR3 + mice, but not DQ8 + mice. Of the four peptides, one, hTg2079, was consistently pathogenic. Thyroiditis was not only produced by adoptive transfer of hTg-primed, hTg2079-activated cells but also by direct immunization with the peptide. These results demonstrate the utility of using this computer-based algorithm with synthetic peptides to help identify pathogenic T cell epitopes on hTg.

Original languageEnglish (US)
Pages (from-to)79-85
Number of pages7
JournalCellular Immunology
Volume229
Issue number2
DOIs
StatePublished - Jun 1 2004

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Keywords

  • Autoimmune thyroiditis
  • DR3-binding peptide
  • HLA-DR3
  • Thyroglobulin
  • Transgene

ASJC Scopus subject areas

  • Immunology

Cite this

Flynn, J. C., McCormick, D. J., Brusic, V., Wan, Q., Panos, J. C., Giraldo, A. A., David, C. S., & Kong, Y. C. M. (2004). Pathogenic human thyroglobulin peptides in HLA-DR3 transgenic mouse model of autoimmune thyroiditis. Cellular Immunology, 229(2), 79-85. https://doi.org/10.1016/j.cellimm.2004.07.002