Department of Statistics, University of Oxford, Oxford, United Kingdom.
Front Immunol. 2019 Oct 15;10:2454. doi: 10.3389/fimmu.2019.02454. eCollection 2019.
The adaptive immune system uses two main types of antigen receptors: T-cell receptors (TCRs) and antibodies. While both proteins share a globally similar β-sandwich architecture, TCRs are specialized to recognize peptide antigens in the binding groove of the major histocompatibility complex, while antibodies can bind an almost infinite range of molecules. For both proteins, the main determinants of target recognition are the complementarity-determining region (CDR) loops. Five of the six CDRs adopt a limited number of backbone conformations, known as the "canonical classes"; the remaining CDR (β3in TCRs and H3 in antibodies) is more structurally diverse. In this paper, we first update the definition of canonical forms in TCRs, build an auto-updating sequence-based prediction tool (available at http://opig.stats.ox.ac.uk/resources) and demonstrate its application on large scale sequencing studies. Given the global similarity of TCRs and antibodies, we then examine the structural similarity of their CDRs. We find that TCR and antibody CDRs tend to have different length distributions, and where they have similar lengths, they mostly occupy distinct structural spaces. In the rare cases where we found structural similarity, the underlying sequence patterns for the TCR and antibody version are different. Finally, where multiple structures have been solved for the same CDR sequence, the structural variability in TCR loops is higher than that in antibodies, suggesting TCR CDRs are more flexible. These structural differences between TCR and antibody CDRs may be important to their different biological functions.
T 细胞受体 (TCR) 和抗体。虽然这两种蛋白质都具有全球相似的β-三明治结构，但 TCR 专门识别主要组织相容性复合体结合槽中的肽抗原，而抗体可以结合几乎无限范围的分子。对于这两种蛋白质，靶标识别的主要决定因素是互补决定区 (CDR) 环。六个 CDR 中的五个采用有限数量的骨架构象，称为“典型类别”；剩下的 CDR（TCR 中的β3 和抗体中的 H3）在结构上更加多样化。在本文中，我们首先更新 TCR 中典型形式的定义，构建一个自动更新的基于序列的预测工具（可在 http://opig.stats.ox.ac.uk/resources 获得），并展示其在大规模测序研究中的应用。鉴于 TCR 和抗体的全球相似性，我们随后检查了它们的 CDR 的结构相似性。我们发现 TCR 和抗体的 CDR 倾向于具有不同的长度分布，并且在它们具有相似长度的情况下，它们主要占据不同的结构空间。在我们发现结构相似性的极少数情况下，TCR 和抗体版本的潜在序列模式是不同的。最后，对于同一 CDR 序列已经解决了多个结构，TCR 环的结构可变性高于抗体，这表明 TCR CDR 更具灵活性。TCR 和抗体 CDR 之间的这些结构差异可能对它们的不同生物学功能很重要。
