Ando Takao, Davies Terry F
Department of Medicine, Mount Sinai School of Medicine, Box 1055, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Clin Dev Immunol. 2005 Jun;12(2):137-43. doi: 10.1080/17402520500078238.
The thyrotropin receptor (TSHR) is a seven transmembrane G-protein linked glycoprotein expressed on the thyroid cell surface and which, under the regulation of TSH, controls the production and secretion of thyroid hormone from the thyroid gland. This membrane protein is also a major target antigen in the autoimmune thyroid diseases. In Graves' disease, autoantibodies to the TSHR (TSHR-Abs) stimulate the TSHR to produce thyroid hormone excessively. In autoimmune thyroid failure, some patients exhibit TSHR-Abs which block TSH action on the receptor. There have been many attempts to generate human stimulating TSHR-mAbs, but to date, only one pathologically relevant human stimulating TSHR-mAb has been isolated. Most mAbs to the TSHR have been derived from rodents immunized with TSHR antigen from bacteria or insect cells. These antigens lacked the native conformation of the TSHR and the resulting mAbs were exclusively blocking or neutral TSHR-mAbs. However, mAbs raised against intact native TSHR antigen have included stimulating mAbs. One such stimulating mAb has demonstrated a number of differences in its regulation of TSHR post-translational processing. These differences are likely to be reflective of TSHR-Abs seen in Graves' disease.
促甲状腺激素受体（TSHR）是一种七跨膜G蛋白偶联糖蛋白，表达于甲状腺细胞表面，在促甲状腺激素（TSH）的调节下，控制甲状腺激素从甲状腺的产生和分泌。这种膜蛋白也是自身免疫性甲状腺疾病的主要靶抗原。在格雷夫斯病中，针对TSHR的自身抗体（TSHR-Abs）刺激TSHR过度产生甲状腺激素。在自身免疫性甲状腺功能减退症中，一些患者表现出阻断TSH对受体作用的TSHR-Abs。人们进行了许多尝试来生成人刺激性TSHR单克隆抗体（mAb），但迄今为止，仅分离出一种与病理相关的人刺激性TSHR-mAb。大多数针对TSHR的mAb源自用来自细菌或昆虫细胞的TSHR抗原免疫的啮齿动物。这些抗原缺乏TSHR的天然构象，所产生的mAb均为阻断性或中和性TSHR-mAb。然而，针对完整天然TSHR抗原产生的mAb中包括刺激性mAb。一种这样的刺激性mAb在其对TSHR翻译后加工的调节方面已表现出许多差异。这些差异可能反映了在格雷夫斯病中所见的TSHR-Abs。
