Recognition of antigenic peptides bound to major histocompatibility complex (MHC) proteins by αβ T cell receptors (TCRs) is a hallmark of T cell mediated immunity. Recent data suggest that variations in TCR binding geometry may influence T cell signaling, which could help explain outliers in relationships between physical parameters such as TCR-pMHC binding affinity and T cell function. Traditionally, TCR binding geometry has been described with simple descriptors such as the crossing angle, which quantifies what has become known as the TCR's diagonal binding mode. However, these descriptors often fail to reveal distinctions in binding geometry that are apparent through visual inspection. To provide a better framework for relating TCR structure to T cell function, we developed a comprehensive system for quantifying the geometries of how TCRs bind peptide/MHC complexes. We show that our system can discern differences not clearly revealed by more common methods. As an example of its potential to impact biology, we used it to reveal differences in how TCRs bind class I and class II peptide/MHC complexes, which we show allow the TCR to maximize access to and "read out" the peptide antigen. We anticipate our system will be of use in not only exploring these and other details of TCR-peptide/MHC binding interactions, but also addressing questions about how TCR binding geometry relates to T cell function, as well as modeling structural properties of class I and class II TCR-peptide/MHC complexes from sequence information. The system is available at https://tcr3d.ibbr.umd.edu/tcr_com or for download as a script.

中文翻译：

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T 细胞受体结合模式的几何特征揭示了类别特异性结合，以最大限度地获取抗原。


αβ T 细胞受体 (TCR) 识别与主要组织相容性复合体 (MHC) 蛋白结合的抗原肽是 T 细胞介导的免疫的标志。最近的数据表明，TCR 结合几何形状的变化可能会影响 T 细胞信号传导，这有助于解释 TCR-pMHC 结合亲和力和 T 细胞功能等物理参数之间关系的异常值。传统上，TCR 结合几何形状是用简单的描述符来描述的，例如交叉角，它量化了所谓的 TCR 的对角线结合模式。然而，这些描述符通常无法揭示通过目视检查显而易见的结合几何形状的区别。为了提供一个更好的框架来将 TCR 结构与 T 细胞功能联系起来，我们开发了一个综合系统来量化 TCR 如何结合肽/MHC 复合物的几何形状。我们证明我们的系统可以识别更常见的方法无法清楚揭示的差异。作为其影响生物学潜力的一个例子，我们用它来揭示 TCR 如何结合 I 类和 II 类肽/MHC 复合物的差异，我们证明这允许 TCR 最大限度地接触和“读出”肽抗原。我们预计我们的系统不仅可用于探索 TCR 肽/MHC 结合相互作用的这些细节和其他细节，还可解决有关 TCR 结合几何结构如何与 T 细胞功能相关的问题，以及对 I 类和 MHC 的结构特性进行建模。来自序列信息的 II 类 TCR 肽/MHC 复合物。该系统可从 https://tcr3d.ibbr.umd.edu/tcr_com 获取或作为脚本下载。