为了做出适当的反应，T细胞在瞬时与抗原呈递细胞的相互作用期间整合复杂的受体刺激序列。尽管已经有人假设这些相互作用的动力学影响T细胞激活的结果，但方法上的限制阻碍了其正式证明。在这里，我们设计了一种光诱导T细胞结合器（LiTE）系统，这是一种目标T细胞受体（TCR）的重组光遗传学工具。 LiTE系统是一种可逆的分子开关，显示了极高的反应性。作为概念证明，我们解析了特定的TCR刺激时间模式如何塑造T细胞激活。我们建立了CD4+ T细胞对间歇性TCR刺激的响应比它们的CD8+ T细胞的同行更有效，并提供证据表明不同的TCR刺激序列编码不同的细胞因子程序。最后，我们展示了LiTE系统可被利用以创建受光激活的双特异性T细胞结合剂并操纵肿瘤细胞的杀伤。总的来说，LiTE系统提供了了解T细胞如何整合TCR刺激并使用高度时空控制诱导T细胞细胞毒性的机会。

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.