Fluorogenic Granzyme A Substrates Enable Real-Time Imaging of Adaptive Immune Cell Activity
Fluorogenic Granzyme A Substrates Enable Real-Time Imaging of Adaptive Immune Cell Activity
复制标题
荧光颗粒酶 A 底物可实现适应性免疫细胞活性的实时成像
DOI：
10.1002/ange.202216142
复制
发表时间：
2023
影响因子：
--
通讯作者：
Cheng Z
中科院分区：
文献类型：
--
作者：
Cheng Z
细胞毒性免疫细胞，包括T淋巴细胞（ctl）和自然杀伤细胞（NK），是宿主抗肿瘤反应的重要组成部分。ctl和NK细胞在识别癌细胞时分泌颗粒酶A (GzmA)；然而，很少有工具能够以高时空分辨率检测活性GzmA的生理水平。本文报道了人GzmA和小鼠GzmA近红外荧光底物的合理设计。从野生型和GzmA敲除小鼠的组织裂解物中可以看出，这些基于活性的探针比其他颗粒酶表现出非常高的催化效率和选择性。此外，我们证明了探针可以实时成像适应性免疫细胞对抗原驱动的癌细胞识别的反应。
Cytotoxic immune cells, including T lymphocytes (CTLs) and natural killer (NK) cells, are essential components of the host response against tumors. CTLs and NK cells secrete granzyme A (GzmA) upon recognition of cancer cells; however, there are very few tools that can detect physiological levels of active GzmA with high spatiotemporal resolution. Herein, we report the rational design of the near‐infrared fluorogenic substrates for human GzmA and mouse GzmA. These activity‐based probes display very high catalytic efficiency and selectivity over other granzymes, as shown in tissue lysates from wild‐type and GzmA knock‐out mice. Furthermore, we demonstrate that the probes can image how adaptive immune cells respond to antigen‐driven recognition of cancer cells in real time.