Nagayama Y, Wadsworth H L, Russo D, Chazenbalk G D, Rapoport B
Thyroid Molecular Biology Unit, Veterans Administration Medical Center, San Francisco, California 94121.
J Clin Invest. 1991 Jul;88(1):336-40. doi: 10.1172/JCI115297.
We examined the relative effects of thyrotropin (TSH) and TSH receptor autoantibodies in the sera of patients with autoimmune thyroid disease on three TSH-lutropin/chorionic gonadotropin (LH/CG) receptor extracellular domain chimeras. Each chimera binds TSH with high affinity. Only the chimera with TSH receptor extracellular domains ABC (amino acids 1-260) had a functional (cAMP) response to thyroid stimulatory IgG. The chimeras with TSH receptor domains CD (amino acids 171-360) and DE (amino acids 261-418) were unresponsive. The lack of response of the chimera with TSH receptor domains DE was anticipated because it fails to transduce a signal with TSH stimulation, unlike the other two chimeras. A different spectrum of responses occurred when the TSH-LH/CG chimeras were examined in terms of autoantibody competition for TSH binding. IgG with TSH binding-inhibitory activity when tested with the wild-type TSH receptor also inhibited TSH binding to the chimera with TSH receptor domains DE. Dramatically, however, these IgG did not inhibit TSH binding to the chimera with TSH receptor domains CD, and had weak or absent activity with the chimera with TSH receptor domains ABC. Chimeras with TSH receptor domains ABC and DE were equally effective in affinity-purifying IgG with thyroid-stimulatory and TSH binding-inhibitory activities. Nonstimulatory IgG with TSH binding-inhibitory activity inhibited the action of stimulatory IgG on the wild-type TSH receptor, but not with the chimera containing TSH receptor domains ABC. In summary, TSH receptor autoantibodies and TSH bind to regions in both domains ABC and DE of the TSH receptor extracellular region. Stimulatory and inhibitory TSH receptor autoantibodies, as well as TSH, appear to bind to different sites in domains ABC, but similar sites in domains DE, of the receptor. Alternatively, TSH and the different TSH receptor antibodies bind with differing affinities to the same site in the ABC region.
我们研究了自身免疫性甲状腺疾病患者血清中的促甲状腺激素（TSH）和TSH受体自身抗体对三种TSH-促黄体生成素/绒毛膜促性腺激素（LH/CG）受体细胞外结构域嵌合体的相对影响。每种嵌合体都能高亲和力结合TSH。只有具有TSH受体细胞外结构域ABC（氨基酸1-260）的嵌合体对甲状腺刺激性IgG有功能性（cAMP）反应。具有TSH受体结构域CD（氨基酸171-360）和DE（氨基酸261-418）的嵌合体无反应。具有TSH受体结构域DE的嵌合体无反应是意料之中的，因为与其他两种嵌合体不同，它在TSH刺激下无法转导信号。当从自身抗体对TSH结合的竞争方面检查TSH-LH/CG嵌合体时，出现了不同的反应谱。在用野生型TSH受体测试时具有TSH结合抑制活性的IgG，也抑制TSH与具有TSH受体结构域DE的嵌合体的结合。然而，显著的是，这些IgG并不抑制TSH与具有TSH受体结构域CD的嵌合体的结合，并且对具有TSH受体结构域ABC的嵌合体活性较弱或无活性。具有TSH受体结构域ABC和DE的嵌合体在亲和纯化具有甲状腺刺激和TSH结合抑制活性的IgG方面同样有效。具有TSH结合抑制活性的非刺激性IgG抑制刺激性IgG对野生型TSH受体的作用，但对含有TSH受体结构域ABC的嵌合体则无此作用。总之，TSH受体自身抗体和TSH结合于TSH受体细胞外区域的结构域ABC和DE中的区域。刺激性和抑制性TSH受体自身抗体以及TSH似乎结合于受体结构域ABC中的不同位点，但结合于结构域DE中的相似位点。或者，TSH和不同的TSH受体抗体以不同亲和力结合于ABC区域中的同一位点。
Zotero 插件