近日，美国芝加哥大学教授田博之和Jun Huang研究团队发现了六足异质结构对T细胞识别的多模态探测。相关论文发表在2024年2月19日出版的《自然—方法学》杂志上。

他们设计了一种仿生抗原呈递系统（bAPS），用于单细胞刺激和T细胞识别的集体调节。bAPS利用由亚微米立方赤铁矿核心（α-Fe2O3）和具有不同表面修饰的纳米结构二氧化硅分支组成的六足异质结构。在单分子分辨率下，展示了单个激动剂肽装载的主要组织相容性复合体引起的T细胞激活；结构相似但仅差一个氨基酸的肽引起的不同T细胞受体（TCR）反应；以及与嵌合抗原受体（CARs）相比，TCRs具有更高的抗原识别敏感性。

他们还展示了磁场诱导的六足异质结构旋转如何增强悬浮T细胞和CAR-T细胞的免疫反应。此外，将bAPS确立为一种精确且可扩展的方法，用于在单细胞水平上识别具有刺激性抗原特异性TCR。因此，他们的多模态bAPS代表了一种独特的生物界面工具，用于研究T细胞识别、信号传导和功能。

据了解，利用单细胞和整体水平的抗原呈递系统进行研究，可以为了解T细胞信号传导和激活提供补充的见解。尽管对于推进基础免疫学和免疫疗法至关重要，但目前缺乏一种能够同时在这两个水平上检查T细胞，特别是能够进行单分子级别操作的合成材料工具包。

附：英文原文

Title: Multimodal probing of T-cell recognition with hexapod heterostructures

Author: Huang, Xiaodan, Meng, Lingyuan, Cao, Guoshuai, Prominski, Aleksander, Hu, Yifei, Yang, Chuanwang, Chen, Min, Shi, Jiuyun, Gallagher, Charles, Cao, Thao, Yue, Jiping, Huang, Jun, Tian, Bozhi

Issue&Volume: 2024-02-19

Abstract: Studies using antigen-presenting systems at the single-cell and ensemble levels can provide complementary insights into T-cell signaling and activation. Although crucial for advancing basic immunology and immunotherapy, there is a notable absence of synthetic material toolkits that examine T cells at both levels, and especially those capable of single-molecule-level manipulation. Here we devise a biomimetic antigen-presenting system (bAPS) for single-cell stimulation and ensemble modulation of T-cell recognition. Our bAPS uses hexapod heterostructures composed of a submicrometer cubic hematite core (α-Fe2O3) and nanostructured silica branches with diverse surface modifications. At single-molecule resolution, we show T-cell activation by a single agonist peptide-loaded major histocompatibility complex; distinct T-cell receptor (TCR) responses to structurally similar peptides that differ by only one amino acid; and the superior antigen recognition sensitivity of TCRs compared with that of chimeric antigen receptors (CARs). We also demonstrate how the magnetic field-induced rotation of hexapods amplifies the immune responses in suspended T and CAR-T cells. In addition, we establish our bAPS as a precise and scalable method for identifying stimulatory antigen-specific TCRs at the single-cell level. Thus, our multimodal bAPS represents a unique biointerface tool for investigating T-cell recognition, signaling and function.

DOI: 10.1038/s41592-023-02165-7

Source: https://www.nature.com/articles/s41592-023-02165-7