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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Algorithms
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Amino Acid Sequence
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Animals
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Binding Sites
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Epitopes, T-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / metabolism
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Female
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HLA-DR Antigens / immunology
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HLA-DR Antigens / metabolism
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HLA-DR Serological Subtypes
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HLA-DR3 Antigen / immunology*
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HLA-DR3 Antigen / metabolism
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Histocytochemistry
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Humans
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Inbred NOD
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Mice, Transgenic
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Molecular Sequence Data
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Peptide Fragments / immunology*
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Peptide Fragments / metabolism
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Specific Pathogen-Free Organisms
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Thyroglobulin / immunology*
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Thyroglobulin / metabolism
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Thyroiditis, Autoimmune / immunology*
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Thyroiditis, Autoimmune / pathology
Substances
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Epitopes, T-Lymphocyte
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HLA-DR Antigens
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HLA-DR Serological Subtypes
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HLA-DR3 Antigen
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HLA-DR8 antigen
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Peptide Fragments
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Thyroglobulin