TY - JOUR
T1 - Primary hormonogenic sites as conserved autoepitopes on thyroglobulin in murine autoimmune thyroiditis
T2 - Role of MHC class II
AU - Wan, Qiang
AU - Motte, Reinhard W.
AU - McCormick, Daniel J.
AU - Fuller, Brian E.
AU - Giraldo, Alvaro A.
AU - David, Chella S.
AU - Kong, Yi Chi M.
N1 - Funding Information:
1This work was supported by grants from NIDDK DK 45960 and from St. John Hospital and Medical Center. Presented in part at the 11th Thyroid Congress, Toronto, Canada, September 10±15, 1995. [Thyroid 5 (Suppl. 1), S7, 1995].
PY - 1997
Y1 - 1997
N2 - A few synthetic peptides corresponding to amino acid sequences on human thyroglobulin (Tg) have been reported to induce moderate thyroiditis or activate mouse Tg (MTg)-primed T cells to transfer thyroiditis in mice susceptible to experimental autoimmune thyroiditis. Using three pairs of 12- mer peptides (1-12, 2549-2560, 2559-2570), with thyroxine (T4) or noniodinated thyronine (TO) at the conserved, hormonogenic site 5, 2553, or 2567 respectively, we reported that iodination was not required for a Tg hormonogenic site to be a thyroiditogenic autoepitope. To determine the relative importance of MHC class II and T cell receptor (TCR) repertoire, we compared two EAT-susceptible k and s (CBA and A.SW) haplotypes and their respective MHC-identical strain (C57BR and SJL) with ~50% genomic deletion of TCR Vβ genes. Whereas k and s strains develop MTg-induced EAT, vigorous immunization with peptides containing T4 or T0 at either 5 or 2553, but not at 2567, led to mild (10-20%) thyroiditis only in some mice of either k strain. TCR Vβ gene differences played a minor role. T cell responses to all peptide pairs were quite similar in CBA and C57BR mice, and both hT0(2553) and hT4(2553) reciprocally primed and stimulated their T cells. In adoptive transfer, SJL mice were somewhat more responsive to peptide activation than A.SW but much weaker than k strains. By comparing T4- and T0-containing peptides in different haplotypes, we show further that antigenicity of conserved hormonogenic sites is intrinsic, dependent more on amino acid sequence and binding to appropriate class II molecules and less on TCR repertoire or iodination of T0.
AB - A few synthetic peptides corresponding to amino acid sequences on human thyroglobulin (Tg) have been reported to induce moderate thyroiditis or activate mouse Tg (MTg)-primed T cells to transfer thyroiditis in mice susceptible to experimental autoimmune thyroiditis. Using three pairs of 12- mer peptides (1-12, 2549-2560, 2559-2570), with thyroxine (T4) or noniodinated thyronine (TO) at the conserved, hormonogenic site 5, 2553, or 2567 respectively, we reported that iodination was not required for a Tg hormonogenic site to be a thyroiditogenic autoepitope. To determine the relative importance of MHC class II and T cell receptor (TCR) repertoire, we compared two EAT-susceptible k and s (CBA and A.SW) haplotypes and their respective MHC-identical strain (C57BR and SJL) with ~50% genomic deletion of TCR Vβ genes. Whereas k and s strains develop MTg-induced EAT, vigorous immunization with peptides containing T4 or T0 at either 5 or 2553, but not at 2567, led to mild (10-20%) thyroiditis only in some mice of either k strain. TCR Vβ gene differences played a minor role. T cell responses to all peptide pairs were quite similar in CBA and C57BR mice, and both hT0(2553) and hT4(2553) reciprocally primed and stimulated their T cells. In adoptive transfer, SJL mice were somewhat more responsive to peptide activation than A.SW but much weaker than k strains. By comparing T4- and T0-containing peptides in different haplotypes, we show further that antigenicity of conserved hormonogenic sites is intrinsic, dependent more on amino acid sequence and binding to appropriate class II molecules and less on TCR repertoire or iodination of T0.
KW - Autoimmune thyroiditis
KW - Experimental autoimmune thyroiditis
KW - Hormonogenic site peptides
KW - Role of MHC
KW - TCRVβ gene deletion
KW - Thyroglobulin
KW - thyroglobulin epitopes
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U2 - 10.1006/clin.1997.4443
DO - 10.1006/clin.1997.4443
M3 - Article
C2 - 9344702
AN - SCOPUS:0030731321
SN - 0090-1229
VL - 85
SP - 187
EP - 194
JO - Clinical Immunology and Immunopathology
JF - Clinical Immunology and Immunopathology
IS - 2
ER -