TY - JOUR
T1 - A novel H2A-E+ transgenic model susceptible to human but not mouse thyroglobulin-induced autoimmune thyroiditis
T2 - Identification of mouse pathogenic epitopes
AU - Brown, Nicholas K.
AU - McCormick, Daniel J.
AU - Brusic, Vladimir
AU - David, Chella S.
AU - Kong, Yi chi M.
PY - 2008
Y1 - 2008
N2 - 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 H2Eb, 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.
AB - 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 H2Eb, 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.
KW - Autoimmunity
KW - Class II transgene
KW - Experimental autoimmune thyroiditis
KW - H2E transgene
KW - Thyroglobulin epitopes
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U2 - 10.1016/j.cellimm.2008.02.002
DO - 10.1016/j.cellimm.2008.02.002
M3 - Article
C2 - 18489063
AN - SCOPUS:44549085898
SN - 0008-8749
VL - 251
SP - 1
EP - 7
JO - Cellular Immunology
JF - Cellular Immunology
IS - 1
ER -