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Fluorogenic Granzyme A Substrates Enable Real-Time Imaging of Adaptive Immune Cell Activity.


ABSTRACT: 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.

SUBMITTER: Cheng Z 

PROVIDER: S-EPMC10953043 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Fluorogenic Granzyme A Substrates Enable Real-Time Imaging of Adaptive Immune Cell Activity.

Cheng Zhiming Z   Thompson Emily J EJ   Mendive-Tapia Lorena L   Scott Jamie I JI   Benson Sam S   Kitamura Takanori T   Senan-Salinas Ana A   Samarakoon Youhani Y   Roberts Edward W EW   Arias Maykel A MA   Pardo Julian J   Galvez Eva M EM   Vendrell Marc M  

Angewandte Chemie (Weinheim an der Bergstrasse, Germany) 20230116 8


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 ve  ...[more]

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