Understanding the Significance and Implications of Antibody Numbering and Antigen-Binding Surface/Residue Definition.
Understanding the Significance and Implications of Antibody Numbering and Antigen-Binding Surface/Residue Definition.
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DOI：
10.3389/fimmu.2018.02278
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发表时间：
2018
影响因子：
7.3
通讯作者：
Vandevenne MS
中科院分区：
文献类型：
--
作者：
Dondelinger M;Filée P;Sauvage E;Quinting B;Muyldermans S;Galleni M;Vandevenne MS
单克隆抗体在人类和动物健康中发挥着越来越重要的作用。蛋白质工程和化学工程的不同策略，包括非人抗体的人源化技术被成功地应用于优化抗体的临床性能。尽管出现了允许开发完全人抗体的技术，例如转基因异种小鼠，但抗体人源化仍然是治疗性抗体的标准程序。抗体人源化的一个重要先决条件是需要标准化的编号方法来精确定义影响抗体-抗原相互作用的结合亲和力和/或特异性的互补决定区（CDR）、框架和来自轻链和重链的残基。最近产生的深度测序数据和越来越多的来自人类和非人类来源的抗体的三维结构的解决导致了许多数据库的出现。然而，这些不同的数据库使用不同的编号惯例和CDR定义。此外，可变链长度的大波动，特别是重链的CDR 3（CDRH 3），几乎不会使抗体序列的比较和分析以及抗原结合残基的鉴定复杂化。本文比较和讨论了迄今为止建立的不同编号方案和“CDR”定义。此外，总结了用于抗体残基编号和CDR残基鉴定的概念和策略。最后，它讨论了特定组的残基在免疫球蛋白的结合亲和力和/或特异性的重要性。
Monoclonal antibodies are playing an increasing role in both human and animal health. Different strategies of protein and chemical engineering, including humanization techniques of non-human antibodies were applied successfully to optimize clinical performances of antibodies. Despite the emergence of techniques allowing the development of fully human antibodies such as transgenic Xeno-mice, antibody humanization remains a standard procedure for therapeutic antibodies. An important prerequisite for antibody humanization requires standardized numbering methods to define precisely complementary determining regions (CDR), frameworks and residues from the light and heavy chains that affect the binding affinity and/or specificity of the antibody-antigen interaction. The recently generated deep-sequencing data and the increasing number of solved three-dimensional structures of antibodies from human and non-human origins have led to the emergence of numerous databases. However, these different databases use different numbering conventions and CDR definitions. In addition, the large fluctuation of the variable chain lengths, especially in CDR3 of heavy chains (CDRH3), hardly complicates the comparison and analysis of antibody sequences and the identification of the antigen binding residues. This review compares and discusses the different numbering schemes and “CDR” definition that were established up to date. Furthermore, it summarizes concepts and strategies used for numbering residues of antibodies and CDR residues identification. Finally, it discusses the importance of specific sets of residues in the binding affinity and/or specificity of immunoglobulins.
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影响因子：
14.9
作者：
Dunbar J;Krawczyk K;Leem J;Marks C;Nowak J;Regep C;Georges G;Kelm S;Popovic B;Deane CM
通讯作者：
Deane CM
影响因子：
5.6
作者：
CHOTHIA, C;LESK, AM
通讯作者：
LESK, AM
DOI：
10.1073/pnas.93.8.3675
发表时间：
1996-04-16
影响因子：
11.1
作者：
Gelfand, IM;Kister, AE;Leshchiner, D
通讯作者：
Leshchiner, D
影响因子：
5.6
作者：
AlLazikani, B;Lesk, AM;Chothia, C
通讯作者：
Chothia, C
影响因子：
3.6
作者：
Abhinandan, K. R.;Martin, Andrew C. R.
通讯作者：
Martin, Andrew C. R.