T cells react to foreign or self-antigens through T cell receptor (TCR) signaling. Several decades of research have delineated the mechanism of TCR signal transduction and its impact on T cell performance. This knowledge provides the foundation for chimeric antigen receptor T cell (CAR-T cell) technology, by which T cells are redirected in a major histocompatibility complex-unrestricted manner. TCR and CAR signaling plays a critical role in determining the T cell state, including exhaustion and memory. Given its artificial nature, CARs might affect or rewire signaling differently than TCRs. A better understanding of CAR signal transduction would greatly facilitate improvements to CAR-T cell technology and advance its usefulness in clinical practice. Herein, we systematically review the knowns and unknowns of TCR and CAR signaling, from the contact of receptors and antigens, proximal signaling, immunological synapse formation, and late signaling outcomes. Signaling through different T cell subtypes and how signaling is translated into practice are also discussed.

T细胞通过T细胞受体（TCR）信号传导与外源或自身抗原发生反应。几十年的研究描述了TCR信号转导的机制及其对T细胞性能的影响。这项知识为嵌合抗原受体T细胞（CAR-T细胞）技术提供了基础，通过该技术，T细胞可以以一种主要的组织相容性复合物不受限制的方式重定向。TCR和CAR信号传导在确定T细胞状态（包括疲劳和记忆）中起着至关重要的作用。鉴于其人为的性质，CAR可能在影响或重新布线信号方面与TCR不同。对CAR信号转导的更好理解将极大地促进CAR-T细胞技术的改进，并提高其在临床实践中的实用性。在这里，我们系统地回顾了TCR和CAR信号传导的已知与未知，受体和抗原的接触，近端信号传导，免疫突触形成和晚期信号传导结局。还讨论了通过不同T细胞亚型发出的信号以及如何将信号转化为实践。