A novel H2A-E+ transgenic model susceptible to human but not mouse thyroglobulin-induced autoimmune thyroiditis: identification of mouse pathogenic epitopes.
The A-E+ transgenic mouse is highly susceptible to human thyroglobulin (hTg)-induced thyroiditis, but strongly tolerant to a challenge by mouse thyroglobulin (mTg), in stark contrast to traditionally susceptible strains, wherein mTg induces stronger thyroiditis. To identify mouse thyroid epitopes recognized by destructive, hTg-primed T cells, we selected the three hTg epitopes known to be presented by H2E(b), as the basis for synthesizing potential mTg epitopes. One 15-mer peptide, mTg409, did prime T cells, elicit Ab, and induce thyroiditis. Moreover, cells primed with corresponding, pathogenic hTg410 cross-reacted with mTg409, and vice versa. mTg409 contained 4/4 anchor residues, similar to the corresponding hTg peptide. Based on this finding, a second mTg epitope, mTg179, was subsequently identified. These mTg autoepitopes, identified by using thyroiditogenic hTg epitopes, help to explain the severe thyroiditis seen in this novel A-E+ transgenic model.
Brown
Nicholas K
NK
Department of Immunology and Microbiology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA.
McCormick
Daniel J
DJ
Brusic
Vladimir
V
David
Chella S
CS
Kong
Yi-Chi M
YC
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000235:genetics*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D013045:Species Specificity; D013954:Thyroglobulin / Q000235:genetics / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*
D006183:H-2 Antigens; D016056:Immunodominant Epitopes; D010455:Peptides; D013954:Thyroglobulin