Anti-idiotypic route to anti-acetylcholine receptor antibodies and experimental myasthenia gravis.
Anti-idiotypic route to anti-acetylcholine receptor antibodies and experimental myasthenia gravis.
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抗乙酰胆碱受体抗体和实验性重症肌无力的抗独特型途径。
DOI：
10.1073/pnas.79.15.4810
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发表时间：
1982
影响因子：
11.1
通讯作者：
Erlanger,BF
中科院分区：
文献类型：
--
作者：
Wassermann,NH;Penn,AS;Freimuth,PI;Treptow,N;Wentzel,S;Cleveland,WL;Erlanger,BF
trans-3,3'-Bis[α-(三甲基铵)甲基]偶氮苯溴化物 (BisQ) 是 Electrophorus electricus 乙酰胆碱受体 (AcChoR) 的有效激动剂。 BisQ 受到高度限制，表明当 AcChoR 处于激活状态时，其结构与 AcChoR 的结合位点互补。兔体内产生的针对牛血清白蛋白和 BisQ 衍生物的缀合物的抗体在多种激动剂的结合顺序以及十甲铵离子（激动剂）相对于六甲铵离子（拮抗剂）的优先识别方面模拟了 AcChoR 的结合特征。用纯化的抗 BisQ 免疫三只兔子产生了具有抗 AcChoR 结合特征的抗血清，通过补体结合和酶免疫测定，在所有三只免疫兔子的血清中都可以证明与来自大鼠、鱼雷和鳗鱼的受体制剂的交叉反应。三只兔子中的两只表现出与 AcChoR 免疫后相似的肌肉无力迹象。其中一只兔子接受了新斯的明肌肉注射，并显示出暂时的改善。另一项研究显示，以 50 Hz 频率刺激坐骨神经后，后肢肌肉出现强直后疲劳。因此，通过用针对AcChoR的有效配体的抗体进行免疫来引发与AcChoR反应的抗体，而无需分离受体本身。类似的机制可能在至少一些自身免疫性疾病的病因学中发挥作用，其中涉及各种其他受体的抗体。
trans-3,3'-Bis[alpha-(trimethylammonio)methyl]azobenzene bromide (BisQ) is a potent agonist of the acetylcholine receptor (AcChoR) of Electrophorus electricus. BisQ is highly constrained, suggesting that its structure is complementary to the combining site of the AcChoR when the latter is in its activated state. Antibodies produced in rabbits to a conjugate of bovine serum albumin and a derivative of BisQ mimicked the binding characteristics of the AcChoR with respect to the order of binding of a variety of agonists and to the preferred recognition of decamethonium ion (an agonist) over hexamethonium ion (an antagonist). Immunization of three rabbits with purified anti-BisQ yielded antisera having binding characteristics of anti-AcChoR in that, by complement fixation and enzyme immunoassay, crossreactions with receptor preparations from rat, Torpedo, and eel could be demonstrated in sera of all three rabbits immunized. Two of the three rabbits showed signs of muscle weakness similar to that seen after immunization with the AcChoR. One of the rabbits was injected intramuscularly with neostigmine and showed temporary improvement. Another showed post-tetanic exhaustion of hind-limb muscles after stimulation of the sciatic nerve at 50 Hz. Antibodies reactive with the AcChoR, therefore, were elicited by immunization with an antibody to a potent ligand of the AcChoR without the necessity of isolating the receptor itself. A similar mechanism may play a part in the etiology of at least some autoimmune diseases in which antibodies to various other receptors are involved.