Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, China.
The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China.
Nat Nanotechnol. 2023 Jul;18(7):818-827. doi: 10.1038/s41565-023-01333-2. Epub 2023 Mar 9.
How the engagement of a T-cell receptor to antigenic peptide-loaded major histocompatibility complex on antigen-presenting cells (APCs) initiates intracellular signalling cascades in T cells is not well understood. In particular, the dimension of the cellular contact zone is regarded as a determinant, but its influence remains controversial. This is due to the need for appropriate strategies for manipulating intermembrane spacing between the APC-T-cell interfaces without involving protein modification. Here we describe a membrane-anchored DNA nanojunction with distinct sizes to extend, maintain and shorten the APC-T-cell interface down to 10 nm. Our results suggest that the axial distance of the contact zone is critical in T-cell activation, presumably by modulating protein reorganization and mechanical force. Notably, we observe the promotion of T-cell signalling by shortening the intermembrane distance.
T 细胞受体与抗原呈递细胞 (APC) 上加载抗原肽的主要组织相容性复合物的结合如何引发 T 细胞内的信号级联反应，目前还不是很清楚。特别是，细胞接触区的大小被认为是一个决定因素，但它的影响仍然存在争议。这是因为需要适当的策略来操纵 APC-T 细胞界面之间的膜间间距，而不涉及蛋白质修饰。在这里，我们描述了一种具有不同尺寸的膜锚定 DNA 纳米结，以将 APC-T 细胞界面延长、维持和缩短至 10nm。我们的结果表明，接触区的轴向距离在 T 细胞激活中是至关重要的，可能是通过调节蛋白质重组和机械力。值得注意的是，我们观察到通过缩短膜间距离来促进 T 细胞信号转导。
