Induction of experimental autoimmune thyroiditis in rats with the synthetic peptide (2495-2511) of thyroglobulin.
Induction of experimental autoimmune thyroiditis in rats with the synthetic peptide (2495-2511) of thyroglobulin.
复制标题
用甲状腺球蛋白的合成肽（2495-2511）诱导大鼠实验性自身免疫性甲状腺炎。
作者：
B. Balasa;G. Carayanniotis
我们先前已经证明，合成的17肽TgP1(A.A.2495-2511)来自大鼠甲状腺球蛋白(TG)序列，在小鼠中是促甲状腺激素的，由T或B细胞水平上的非免疫显性但高度免疫原性决定簇组成。尽管TgP1似乎在系统发育上是保守的，但由于小鼠的TG氨基酸序列尚不清楚，因此它在小鼠体内是否为自体多肽仍不确定。在这份报告中，我们证明了TgP1还可以在WKY、F344和WF品系的大鼠中诱导实验性自身免疫性甲状腺炎(EAT)，这些品系在TG攻击后是已知的易感品系。用TgP1免疫所有毒株，在体外都能引起增殖的淋巴细胞对该多肽产生强烈的反应，而这些反应可被抗CD4、OX-6和OX-17决定簇的单抗所消除，这表明TgP1可被第II类限制性T细胞识别。在体内，用自体或异源TG启动，在体外没有导致TgP1特异性的增殖，证实了这一序列在大鼠中的隐蔽性质。与在小鼠中的发现相反，尽管存在EAT，但在大鼠中没有观察到强烈的多肽特异性免疫球蛋白反应。这些数据表明，TgP1在自体系统中是免疫致病的，并首次为大鼠体内存在明确的自体抗原性TG肽提供了证据。
We have previously shown that the synthetic 17 mer peptide TgP1 (a.a. 2495-2511) from the rat thyroglobulin (Tg) sequence is thyroiditogenic in mice and consists of nonimmunodominant but highly immunogenic determinants at the T or B cell level. Although TgP1 appears to be phylogenetically conserved, it remains uncertain whether it is a self-peptide in mice since the mouse Tg amino acid sequence is unknown. In this report, we demonstrate that TgP1 also induces experimental autoimmune thyroiditis (EAT) in WKY, F344, and WF strains of rats that are known to be EAT-susceptible after Tg challenge. Priming of all strains with TgP1 led to strong proliferative lymph node cell responses to the peptide in vitro that were abrogated by MAbs against CD4, OX-6, and OX-17 determinants, suggesting TgP1 recognition by class II-restricted T cells. In vivo priming with autologous or heterologous Tg did not lead to TgP1-specific proliferation in vitro confirming the cryptic nature of this sequence in rats. In contrast to findings in the mouse, strong peptide-specific IgG responses were not observed in rats despite the presence of EAT. These data demonstrate that TgP1 is immunopathogenic in an autologous system and provide the first evidence of a defined autoantigenic Tg peptide in rats.