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首页> 外文期刊>Infection and immunity >Neutralization of tetanus toxin by distinct monoclonal antibodies binding to multiple epitopes on the toxin molecule.
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Neutralization of tetanus toxin by distinct monoclonal antibodies binding to multiple epitopes on the toxin molecule.

机译：通过与毒素分子上多个表位结合的独特单克隆抗体中和破伤风毒素。

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Fifty-seven hybridomas producing antibodies to tetanus toxoid or to the Ibc or B-IIb fragment of the toxin were isolated independently. Competitive inhibition studies demonstrated that monoclonal antibodies from mice immunized with the toxoid bound to at least 20 different epitopes on the toxoid molecule. Similar competitive binding studies revealed eight distinct epitopes on the B-IIb fragment and three to five epitopes on the Ibc fragment of the toxin. Neutralization of toxicity was effected by nine distinct monoclonal antibodies from hybridomas of toxoid-immunized mice and by one monoclonal antibody from B-IIb-immunized mice. Mixtures of two, three, and four different monoclonal antibodies in a variety of combinations exerted a synergistic effect of ca. 200-fold over that observed with individual monoclonal antibodies, indicating that efficient neutralization may involve the simultaneous binding of at least two antibody molecules to different specific regions of the toxin molecule. Only one toxoid-induced monoclonal antibody failed to bind to tetanus toxin. All neutralizing antibodies bound to epitopes on the heavy chain of tetanus toxin. Six of these were directed toward epitopes on the NH2-terminal half, whereas four bound to epitopes on the carboxy-terminal half of the heavy chain. Only one monoclonal antibody bound preferentially to the light chain, but two other monoclonal antibodies appeared to bind to both chains, indicating some homology between these two chains.
机译：独立分离出57种产生针对破伤风类毒素或毒素的Ibc或B-IIb片段的抗体的杂交瘤。竞争性抑制研究表明，用类毒素免疫的小鼠单克隆抗体与类毒素分子上的至少20个不同表位结合。相似的竞争结合研究表明，毒素的B-IIb片段上有8个不同的表位，而Ibc片段上有3至5个表位。毒性的中和是通过类毒素免疫小鼠杂交瘤中的九种不同单克隆抗体和一种B-IIb免疫小鼠中的单克隆抗体来实现的。两种，三种和四种不同单克隆抗体在各种组合中的混合物发挥了ca的协同作用。比单个单克隆抗体观察到的抗体高200倍，表明有效的中和可能涉及至少两个抗体分子同时与毒素分子的不同特定区域结合。只有一种类毒素诱导的单克隆抗体无法结合破伤风毒素。所有中和抗体都与破伤风毒素重链上的表位结合。这些中的六个针对于NH 2末端一半上的表位，而四个与重链的羧基末端一半上的表位结合。仅一种单克隆抗体优先与轻链结合，但是其他两种单克隆抗体似乎与两条链结合，表明这两条链之间有些同源。

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