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首页> 外文期刊>Cytokine >A neutralizing monoclonal antibody specific for the dimer interface region of IL-8.
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A neutralizing monoclonal antibody specific for the dimer interface region of IL-8.

机译：对IL-8的二聚体界面区域具有特异性的中和单克隆抗体。

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摘要

We have generated two mAbs, 6G4.2.5 and A5.12.14, that are similarly capable of neutralizing the biologic activity of wild-type IL-8. To characterize these antibodies further, their reactivity against a series of engineered IL-8 monomer and dimer variants was examined using a neutrophil degranulation assay. While 6G4.2.5 was found to block effectively the biologic activity of all variants regardless of their dimerization status, the results for A5.12.14 differed dramatically. A5.12.14 fully inhibited the agonist activity of one of the monomer variants, partially blocked the activity of another, and had no effect on the activity of two other variants. These results suggested that the binding epitope of A5.12.14 was being affected by the particular amino acid substitutions introduced into the dimer interface region of the variants to disfavor dimerization. If A5.12.14 indeed binds to the dimer interface region of IL-8, it could be predicted that this mAb would be unable to inhibit the activity of dimeric IL-8. This was confirmed in studies which showed that A5.12.14 had no demonstrable effect on the activity of a constitutively dimeric IL-8 variant. These studies represent the first example of a mAb specific for the dimerization status of IL-8. Copyright 2000 Academic Press.
机译：我们已经产生了两个mAb，即6G4.2.5和A5.12.14，它们具有类似的中和野生型IL-8生物学活性的能力。为了进一步表征这些抗体，使用嗜中性粒细胞脱粒试验检测了它们对一系列工程化IL-8单体和二聚体变体的反应性。尽管发现6G4.2.5有效阻止所有变体的生物活性，而不管其二聚化状态如何，但A5.12.14的结果却截然不同。 A5.12.14完全抑制了一个单体变体的激动剂活性，部分阻断了另一个变体的活性，并且对另外两个变体的活性没有影响。这些结果表明，A5.12.14的结合表位受到引入变体二聚体界面区域的特定氨基酸取代的影响，从而不利于二聚化。如果A5.12.14确实结合到IL-8的二聚体界面区域，则可以预测该mAb将无法抑制二聚体IL-8的活性。在研究中证实了这一点，该研究表明A5.12.14对组成型二聚体IL-8变体的活性没有可证明的作用。这些研究代表了针对IL-8二聚化状态的mAb的第一个实例。版权所有2000学术出版社。

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