| Autor: |
Morgane Jaeger, Amandine Anastasio, Sophie Brustlein, Renaud Vincentelli, Fabien Durbesson, Rémy Char, Maud Boussand, Mathias Lechelon, Rafael J. Argüello, Didier Marguet, Hai-Tao He, Rémi Lasserre |
| Přispěvatelé: |
Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), He, Hai-Tao |
| Rok vydání: |
2022 |
| Předmět: |
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| DOI: |
10.1101/2022.04.15.488452 |
| Popis: |
To mount appropriate responses, T cells integrate complex sequences of receptor stimuli perceived during transient interactions with antigen presenting cells. Although it has been hypothesized that the dynamics of these interactions influence the outcome of T cell activation, methodological limitations have hindered its formal demonstration. Here, we have engineered the Light-inducible T cell engager (LiTe) system, a recombinant optogenetics-based molecular tool targeting the T Cell Receptor (TCR). The LiTe system constitutes a reversible molecular switch displaying exquisite reactivity. As proof of concept, we dissect how specific temporal patterns of TCR stimulation shape T cell activation patterns. We established that CD4+ T cells respond to intermittent TCR stimulation more efficiently than their CD8+ T cells counterparts and provide evidence that distinct sequences of TCR stimulation encode different cytokine programs. Finally, we show that the LiTe system could be exploited to create light-activated bispecific T cell engagers and manipulate tumor cell killing. Overall, the LiTe system provides new opportunities to understand how T cells integrate TCR stimulations and to trigger T cell cytotoxicity with a high spatiotemporal control. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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