Variable Region Identical Immunoglobulins Differing in Isotype Express Different Paratopes
Variable Region Identical Immunoglobulins Differing in Isotype Express Different Paratopes
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DOI：
10.1074/jbc.m112.404483
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发表时间：
2012-10-12
影响因子：
4.8
通讯作者：
Casadevall, Arturo
中科院分区：
文献类型：
--
作者：
Janda, Alena;Eryilmaz, Ertan;Casadevall, Arturo
抗体（Ab）恒定（C）区可以影响精细特异性的发现表明，同种型转换有助于产生Ab多样性和独特型限制。尽管该观察结果对于不同的免疫学效应（如疫苗应答、同种型限制性抗体应答以及原发性和继发性应答的起源）具有中心意义，但导致该现象的分子机制尚不清楚。在这项研究中，我们已经采取了一种新的方法来解决这个问题，探测的互补位与N-15标签肽模拟物，然后通过核磁共振光谱和荧光发射光谱。具体而言，我们已经探索了C区对可变（V）区施加构象约束以影响V区相同IgG（1）、IgG（2a）、IgG（2b）和IgG（3）mAb中的互补位结构的假设。结果揭示了同种型相关的差异，在荧光发射光谱和温度相关的差异，结合和切割的肽模拟物。我们的结论是，C区可以修改V区的结构，改变抗体的互补位，从而提供了一个解释同种型如何影响抗体的特异性。
The finding that the antibody (Ab) constant (C) region can influence fine specificity suggests that isotype switching contributes to the generation of Ab diversity and idiotype restriction. Despite the centrality of this observation for diverse immunological effects such as vaccine responses, isotype-restricted antibody responses, and the origin of primary and secondary responses, the molecular mechanism(s) responsible for this phenomenon are not understood. In this study, we have taken a novel approach to the problem by probing the paratope with N-15 label peptide mimetics followed by NMR spectroscopy and fluorescence emission spectroscopy. Specifically, we have explored the hypothesis that the C region imposes conformational constraints on the variable (V) region to affect paratope structure in a V region identical IgG(1), IgG(2a), IgG(2b), and IgG(3) mAbs. The results reveal isotype-related differences in fluorescence emission spectroscopy and temperature-related differences in binding and cleavage of a peptide mimetic. We conclude that the C region can modify the V region structure to alter the Ab paratope, thus providing an explanation for how isotype can affect Ab specificity.