Geometrical characterization of T cell receptor binding modes reveals class-specific binding to maximize access to antigen.
Geometrical characterization of T cell receptor binding modes reveals class-specific binding to maximize access to antigen.
复制标题
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。
DOI：
10.1002/prot.25829
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发表时间：
2020
期刊：
影响因子：
2.9
通讯作者：
Baker,BrianM
中科院分区：
文献类型：
--
作者：
Singh,NishantK;Abualrous,EsamT;Ayres,CoryM;Noé,Frank;Gowthaman,Ragul;Pierce,BrianG;Baker,BrianM
αβ T细胞受体（TCR）对与主要组织相容性复合体（MHC）蛋白结合的抗原肽的识别是T细胞介导的免疫的标志。最近的数据表明，TCR结合几何结构的变化可能会影响T细胞信号传导，这可能有助于解释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结合几何形状已经用简单的描述符如交叉角来描述，交叉角量化了已知的TCR的对角结合模式。然而，这些描述符通常不能揭示通过目视检查明显的装订几何结构的区别。为了提供一个更好的框架，将TCR结构与T细胞功能联系起来，我们开发了一个全面的系统，用于量化TCR如何结合肽/MHC复合物的几何形状。我们表明，我们的系统可以识别更常见方法无法清楚揭示的差异。作为其影响生物学的潜力的一个例子，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，我们表明这允许TCR最大限度地接近和“读出”肽抗原。我们预计我们的系统将不仅用于探索TCR-肽/MHC结合相互作用的这些和其他细节，而且还解决了TCR结合几何结构如何与T细胞功能相关的问题，以及从序列信息中建模I类和II类TCR-肽/MHC复合物的结构特性。该系统可在https://tcr3d.ibbr.umd.edu/tcr_com上获得或作为脚本下载。
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.