Monoclonal antibodies bind with high specificity to a wide range of diverse antigens, primarily mediated by their hypervariable complementarity determining regions (CDRs). The defined antigen binding loops are supported by the structurally conserved β-sandwich framework of the light chain (LC) and heavy chain (HC) variable regions. The LC genes are encoded by two separate loci, subdividing the entity of antibodies into kappa (LCκ) and lambda (LCλ) isotypes that exhibit distinct sequence and conformational preferences. In this work, a diverse set of techniques were employed including machine learning, force field analysis, statistical coupling analysis and mutual information analysis of a non-redundant antibody structure collection. Thereby, it was revealed how subtle changes between the structures of LCκ and LCλ isotypes increase the diversity of antibodies, extending the predetermined restrictions of the general antibody fold and expanding the diversity of antigen binding. Interestingly, it was found that the characteristic framework scaffolds of κ and λ are stabilized by diverse amino acid clusters that determine the interplay between the respective fold and the embedded CDR loops. In conclusion, this work reveals how antibodies use the remarkable plasticity of the beta-sandwich Ig fold to incorporate a large diversity of CDR loops.

中文翻译：

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人抗体λ和κ轻链结构对CDR库的适应性。

单克隆抗体主要与它们的高变互补决定区（CDR）介导，能与多种多样的抗原高特异性结合。定义的抗原结合环由轻链（LC）和重链（HC）可变区的结构保守的β-三明治框架支持。LC基因由两个单独的基因座编码，将抗体的实体分为表现出不同序列和构象偏好的κ（LCκ）和λ（LCλ）同种型。在这项工作中，采用了多种技术，包括机器学习，力场分析，统计耦合分析和非冗余抗体结构集合的相互信息分析。从而，揭示了LCκ和LCλ同种型之间微妙的变化如何增加抗体的多样性，扩展了一般抗体折叠的预定限制并扩大了抗原结合的多样性。有趣的是，发现κ和λ的特征框架支架被决定各个折叠和嵌入的CDR环之间相互作用的多种氨基酸簇所稳定。总之，这项工作揭示了抗体如何利用β-三明治Ig折叠的非凡可塑性来整合多种CDR环。已经发现，κ和λ的特征框架支架被决定各个折叠和嵌入的CDR环之间相互作用的多种氨基酸簇稳定。总之，这项工作揭示了抗体如何利用β-三明治Ig折叠的非凡可塑性来整合多种CDR环。已经发现，κ和λ的特征框架支架被决定各个折叠和嵌入的CDR环之间相互作用的多种氨基酸簇稳定。总之，这项工作揭示了抗体如何利用β-三明治Ig折叠的非凡可塑性来整合各种CDR环。