Abstract：
T cell receptor (TCR) clustering and formation of an immune synapse are crucial for TCR signaling. However, limited information is available about these dynamic assemblies and their connection to transmembrane signaling. In this work, TCR clustering is controlled via plug-and-play nanotools based on an engineered irreversible conjugation pair and a peptide-loaded major histocompatibility complex (pMHC) molecule to compare receptor assembly in a ligand (pMHC)-induced or ligand-independent manner. A streptavidin-binding peptide displayed in both tools enabled their anchoring in streptavidin-pre-structured matrices. Strikingly, pMHC-induced clustering in the confined regions exhibit higher density and dynamics than the ligand-free approach, indicating that the size and architecture of the pMHC ligand influences TCR assembly. This approach enables the control of membrane receptor clustering with high specificity and provides the possibility to explore different modalities of receptor activation.
摘要：
T细胞受体(TCR)聚集和免疫突触的形成对于TCR信号传导是至关重要的。然而,关于这些动态组件及其与跨膜信号传导的联系的信息有限。这里,我们通过基于工程化的不可逆缀合对和负载肽的主要组织相容性复合物（pMHC）分子的即插即用纳米工具来控制TCR聚类，以比较配体（pMHC）诱导或不依赖配体的方式的受体组装。两种工具中展示的链霉亲和素结合肽使其能够锚定在链霉亲和素-预结构化基质中。引人注目的是，pMHC诱导的聚集在限制区域表现出比无配体方法更高的密度和动力学，表明pMHC配体的大小和结构影响TCR组装。我们的方法能够以高特异性控制膜受体聚类，并提供探索受体激活的不同模式的可能性。本文受版权保护。保留所有权利。
