A region on the human thyrotropin receptor which can induce antibodies that inhibit thyrotropin-mediated activation of in vitro thyroid cell function also contains a highly immunogenic epitope.
A region on the human thyrotropin receptor which can induce antibodies that inhibit thyrotropin-mediated activation of in vitro thyroid cell function also contains a highly immunogenic epitope.
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人促甲状腺素受体上的一个区域可以诱导抑制促甲状腺素介导的体外甲状腺细胞功能激活的抗体，也含有高度免疫原性的表位。
DOI：
10.1006/jaut.1994.1034
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发表时间：
1994
影响因子：
12.8
通讯作者：
Prabhakar,BS
中科院分区：
文献类型：
--
作者：
Dallas,JS;Seetharamaiah,GS;Cunningham,SJ;Goldblum,RM;Desai,RK;Prabhakar,BS
促甲状腺激素受体（TSHr）的自身抗体结合到TSHr（ETSHr）的细胞外结构域，并刺激或抑制甲状腺细胞功能和/或生长。为了研究促甲状腺激素受体（TSHR）免疫应答的调节和特异性，本实验室利用杆状病毒表达系统制备了重组人促甲状腺激素受体（ETSHr）蛋白。在本研究中，我们使用了重组ETSHr蛋白，一组重叠的合成肽来源于TSHr，和多克隆兔抗体产生的重组ETSHr和合成肽，以确定一个高度免疫原性的区域（aa 352-388）的TSHr。此外，我们使用竞争性抑制研究来鉴定ETSHr抗体反应的该区域内的优势表位（aa 367-372）。当与其他糖蛋白激素受体相比时，该免疫显性表位位于TSHr特有的区域内。这些数据，连同早期的观察，即针对aa区域357-372的抗体可以抑制促甲状腺激素（TSH）介导的培养中甲状腺细胞的活化，表明aa 367-372代表了TSH r所特有的功能重要区域内的免疫显性表位。因此，该区域可能在诱导或调节针对TSHr的特异性免疫应答中起重要作用。
Autoantibodies to the thyrotropin receptor (TSHr) bind to the extracellular domain of the TSHr (ETSHr) and either stimulate of inhibit thyroid cell function and/or growth. In order to investigate the regulation and the specificity of the immune response to the TSHr, our laboratory recently produced recombinant human ETSHr protein by using the baculovirus expression system. In the present study, we used the recombinant ETSHr protein, a panel of overlapping synthetic peptides derived from the TSHr, and polyclonal rabbit antibodies produced against recombinant ETSHr and synthetic peptides to define a highly immunogenic region (aa 352-388) of the TSHr. Moreover, we used competitive inhibition studies to identify a dominant epitope (aa 367-372) within this region to which ETSHr antibodies react. This immunodominant epitope lies within a region unique to the TSHr when compared to the other glycoprotein hormone receptors. These data, together with the earlier observation that antibodies against aa region 357-372 can inhibit thyrotropin (TSH)-mediated activation of thyroid cells in culture, show that aa 367-372 represents, an immunodominant epitope within a functionally important region which is unique to the TSHr. Therefore, this region may play an important role in the induction or modulation of the specific immune response against the TSHr.