Pathogenic human thyroglobulin peptides in HLA-DR3 transgenic mouse model of autoimmune thyroiditis |
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Authors: | Flynn Jeffrey C McCormick Daniel J Brusic Vladimir Wan Qiang Panos John C Giraldo Alvaro A David Chella S Kong Yi-chi M |
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Institution: | Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA. |
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Abstract: | To identify pathogenic epitopes on human thyroglobulin (hTg), a homodimer of 660kDa, 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. |
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Keywords: | Autoimmune thyroiditis HLA-DR3 Transgene Thyroglobulin DR3-binding peptide |
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