Pathogenic human thyroglobulin peptides in HLA-DR3 transgenic mouse model of autoimmune thyroiditis.
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.
Flynn
Jeffrey C
JC
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
McCormick
Daniel J
DJ
Brusic
Vladimir
V
Wan
Qiang
Q
Panos
John C
JC
Giraldo
Alvaro A
AA
David
Chella S
CS
Kong
Yi-chi M
YC
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D059810:HLA-DR Serological Subtypes; D015803:HLA-DR3 Antigen / Q000276:immunology* / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013954:Thyroglobulin / Q000276:immunology* / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000473:pathology
D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; D015803:HLA-DR3 Antigen; C041559:HLA-DR8 antigen; D010446:Peptide Fragments; D013954:Thyroglobulin