Publication: Light-inducible T cell engagers trigger, tune, and shape the activation of primary T cells.

Published in: Proc Natl Acad Sci U S A 2023 Sep; 120(39): e2302500120

Authors: Jaeger M, Anastasio A, Chamy L, Brustlein S, Vincentelli R, Durbesson F, Gigan J, Thépaut M, Char R, Boussand M, Lechelon M, Argüello RJ, Marguet D, He HT, Lasserre R

Summary

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. 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 opportunities to understand how T cells integrate TCR stimulations and to trigger T cell cytotoxicity with high spatiotemporal control.

Link to Pubmed [PMID] – 37722050

Link to DOI – 10.1073/pnas.2302500120