Using Global Analysis to Extend the Accuracy and Precision of Binding Measurements with T cell Receptors and Their Peptide/MHC Ligands.
Using Global Analysis to Extend the Accuracy and Precision of Binding Measurements with T cell Receptors and Their Peptide/MHC Ligands.
复制标题
使用全局分析来扩展与T细胞受体及其肽/MHC配体的结合测量的准确性和精度。
DOI：
10.3389/fmolb.2017.00002
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发表时间：
2017
影响因子：
5
通讯作者：
Baker BM
中科院分区：
文献类型：
--
作者：
Blevins SJ;Baker BM
在细胞免疫中，克隆分布的 T 细胞受体 (TCR) 与与主要组织相容性复合体蛋白 (pMHC) 结合的肽复合物结合。在 TCR 与 pMHC 的相互作用中，受限和可变多样性区域以结构复杂的方式排列。许多研究利用诱变来试图了解各种界面成分在确定 TCR 识别特性（例如特异性和交叉反应性）中所扮演的“角色”。然而，这些测量通常很复杂，甚至由于 TCR 对 pMHC 的亲和力较弱而受到影响。在这里，我们演示了如何使用多个数据集的全局分析来显着提高此类 TCR 结合实验的准确性和精确度。这种方法的应用应该会对理解 TCR 识别的努力产生积极影响，并促进突变数据库的创建，以帮助设计具有调整的分子识别特性的 TCR。我们还展示了如何使用全局分析来分析 TCR-pMHC 界面中的双突变周期，这可以为免疫识别带来新的见解。
In cellular immunity, clonally distributed T cell receptors (TCRs) engage complexes of peptides bound to major histocompatibility complex proteins (pMHCs). In the interactions of TCRs with pMHCs, regions of restricted and variable diversity align in a structurally complex fashion. Many studies have used mutagenesis to attempt to understand the “roles” played by various interface components in determining TCR recognition properties such as specificity and cross-reactivity. However, these measurements are often complicated or even compromised by the weak affinities TCRs maintain toward pMHC. Here, we demonstrate how global analysis of multiple datasets can be used to significantly extend the accuracy and precision of such TCR binding experiments. Application of this approach should positively impact efforts to understand TCR recognition and facilitate the creation of mutational databases to help engineer TCRs with tuned molecular recognition properties. We also show how global analysis can be used to analyze double mutant cycles in TCR-pMHC interfaces, which can lead to new insights into immune recognition.