用近距离标记扩增抗原诱导的细胞反应，这一成果由中国科学院分子细胞科学卓越创新中心韩硕团队经过不懈努力而取得。相关论文于2025年9月10日发表在《自然》杂志上。

在这里，课题组研究人员重新利用近距离标记（一种以生物素化和识别空间近端蛋白质为主题的方法），将设计的探针扩增为细胞表面的合成抗原细胞。课题组人员开发了一种由红光或超声控制的体内近距离标记技术，在靶抗原附近高密度共价标记荧光素探针。使用T 以细胞受体为例，该团队证明了扩增的荧光素有效地聚集和引导荧光素结合的双特异性T细胞接合剂诱导增强T细胞活化和细胞毒性。非侵入性，组织选择性标记在多个同基因同源肿瘤模型产生有效的免疫反应，迅速根除治疗肿瘤。有效的细胞裂解进一步促进表位扩散，诱导对未治疗的远端病变的全身免疫和对再挑战的免疫记忆。因此，接近标记化学有望作为一种通用策略来操纵抗原依赖性受体功能和细胞状态。

研究人员表示，抗原诱导的细胞表面受体(包括T细胞受体和Fc受体，代表了细胞信号激活的广泛机制。然而，大多数天然存在的抗原，如肿瘤相关抗原，由于密度不足，只能刺激有限的受体凝固和靶反应。

附：英文原文

Title: Amplifying antigen-induced cellular responses with proximity labelling

Author: Li, Shuojun, Men, Yinghui, Wang, Zihan, Wu, Yingcheng, Sun, Hao, Yin, Mingyang, Fan, Xinrui, Deng, Guiyun, Yang, Zhicheng, Yang, Tiange, Xiao, Yudian, Zhou, Hu, Wang, Guangchuan, Fan, Jia, Xu, Chenqi, Gao, Qiang, Han, Shuo

Issue&Volume: 2025-09-10

Abstract: Antigen-induced clustering of cell surface receptors, including Tcell receptors and Fc receptors, represents a widespread mechanism in cell signalling activation1,2. However, most naturally occurring antigens, such as tumour-associated antigens, stimulate limited receptor clustering and on-target responses owing to insufficient density3,4,5. Here we repurpose proximity labelling6, a method used to biotinylate and identify spatially proximal proteins, to amplify designed probes as synthetic antigen clusters on the cell surface. We develop an in vivo proximity-labelling technology controlled by either red light or ultrasound to covalently tag fluorescein probes at high density near a target antigen. Using Tcell receptors as an example, we demonstrate that the amplified fluorescein effectively clusters and directs a fluorescein-binding bispecific Tcell engager to induce enhanced Tcell activation and cytotoxicity. Noninvasive, tissue-selective labelling in multiple syngeneic mouse tumour models produces potent immune responses that rapidly eradicate treated tumours. Efficient cell lysis further promotes epitope spreading to induce systemic immunity against untreated distal lesions and immune memory against rechallenge. Thus, proximity-labelling chemistry holds promise as a generalized strategy to manipulate antigen-dependent receptor function and cell states.

DOI: 10.1038/s41586-025-09518-6

Source: https://www.nature.com/articles/s41586-025-09518-6