Tahara K, Ban T, Minegishi T, Kohn L D
Section on Cell Regulation, National Institute of Diabetes and Kidney and Digestive Diseases, National Institutes of Health, Bethesda, MD 20892.
Biochem Biophys Res Commun. 1991 Aug 30;179(1):70-7. doi: 10.1016/0006-291x(91)91335-a.
To examine the identity of binding sites for thyrotropin (TSH) and thyroid stimulating antibodies (TSAbs) associated with Graves' disease, we constructed eight human TSH receptor/rat LH-CG receptor chimeras. Substitution of amino acid residues 8-165 of the TSH receptor with the corresponding LH-CG receptor segment (Mc1 + 2) results in a chimera which retains high affinity TSH binding and the cAMP response to TSH but loses both the cAMP response to Graves' IgG and Graves' IgG inhibition of TSH binding. Two of three IgGs from idiopathic myxedema patients which contain thyroid stimulation blocking antibodies (TSBAbs) still, however, react with this chimera. Chimeras which substitute residues 90-165 (Mc2) and 261-370 (Mc4) retain the ability to interact with TSH, Graves' IgG, and idiopathic myxedema IgG. The data thus suggest that residues 8-165 contain an epitope specific for TSAbs and that TSH receptor determinants important for the activities of TSAbs and TSH are not identical. Further, binding sites for TSBAbs in idiopathic myxedema may be different from receptor binding sites for both Graves' IgG TSAb as well as TSH and may be different in individual patients.
为了研究促甲状腺激素（TSH）与格雷夫斯病相关的甲状腺刺激抗体（TSAbs）的结合位点的特性，我们构建了8种人TSH受体/大鼠促黄体生成素-绒毛膜促性腺激素（LH-CG）受体嵌合体。用相应的LH-CG受体片段（Mc1 + 2）替换TSH受体的氨基酸残基8-165，产生了一种嵌合体，它保留了对TSH的高亲和力结合以及对TSH的cAMP反应，但失去了对格雷夫斯病IgG的cAMP反应和格雷夫斯病IgG对TSH结合的抑制作用。然而，来自特发性黏液性水肿患者的三种IgG中有两种含有甲状腺刺激阻断抗体（TSBAbs），它们仍然与这种嵌合体反应。替换残基90-165（Mc2）和261-370（Mc4）的嵌合体保留了与TSH、格雷夫斯病IgG和特发性黏液性水肿IgG相互作用的能力。因此，数据表明残基8-165包含一个对TSAbs特异的表位，并且对于TSAbs和TSH的活性重要的TSH受体决定簇并不相同。此外，特发性黏液性水肿中TSBAbs的结合位点可能与格雷夫斯病IgG TSAb以及TSH的受体结合位点不同，并且在个体患者中可能也不同。
