CD8 T 细胞反应是由细胞间受体：配体相互作用调节的精心策划的过程。这些相互作用关键控制着 CD8 T 细胞群的动态，这对于克服病毒感染或癌症等威胁至关重要。然而，控制这些动态的机制仍未完全阐明。在这里，我们确定了在细胞毒性 T 细胞反应启动过程中 CD8 T 细胞上的自连接表面受体 SLAMF7 (CD319) 的迄今为止未知的 T 细胞参考功能。根据其在 T 效应细胞上的细胞毒性相关表达，我们发现 CD8 T 细胞可以利用 SLAMF7 将环境信号转导为细胞相互作用和信息交换。事实上，SLAMF7 促进了稳定同型接触的剂量依赖性形成，最终导致稳定的细胞接触、群体群体以及对扩增和分化的承诺。使用下拉分析和网络分析，我们鉴定了新型 SLAMF7 结合细胞内信号分子，包括 CRK、CRKL 和 Nck 接头，它们参与 T 细胞接触形成，并可能介导 SLAMF7 的传感和粘附功能。因此，在 CD8 T 细胞的抗原识别过程中提供 SLAMF7 信号增强了它们的整体强度，特别是在对低亲和力抗原的反应中，从而显着增强了它们的增殖和细胞毒性能力。总体而言，我们已经确定并表征了细胞毒性 T 淋巴细胞反应程序的有效启动子，并揭示了改进 CD8 T 细胞针对弱病毒或肿瘤相关抗原的反应决策的先进机制，从而加强了我们对此类对手的防御。© 2024。作者。

CD8+ T-cell responses are meticulously orchestrated processes regulated by intercellular receptor:ligand interactions. These interactions critically control the dynamics of CD8+ T-cell populations that is crucial to overcome threats such as viral infections or cancer. Yet, the mechanisms governing these dynamics remain incompletely elucidated. Here, we identified a hitherto unknown T-cell referred function of the self-ligating surface receptor SLAMF7 (CD319) on CD8+ T cells during initiation of cytotoxic T-cell responses. According to its cytotoxicity related expression on T effector cells, we found that CD8+ T cells could utilize SLAMF7 to transduce environmental cues into cellular interactions and information exchange. Indeed, SLAMF7 facilitated a dose-dependent formation of stable homotypic contacts that ultimately resulted in stable cell-contacts, quorum populations and commitment to expansion and differentiation. Using pull-down assays and network analyses, we identified novel SLAMF7-binding intracellular signaling molecules including the CRK, CRKL, and Nck adaptors, which are involved in T-cell contact formation and may mediate SLAMF7 functions in sensing and adhesion. Hence, providing SLAMF7 signals during antigen recognition of CD8+ T cells enhanced their overall magnitude, particularly in responses towards low-affinity antigens, resulting in a significant boost in their proliferation and cytotoxic capacity. Overall, we have identified and characterized a potent initiator of the cytotoxic T lymphocyte response program and revealed advanced mechanisms to improve CD8+ T-cell response decisions against weak viral or tumor-associated antigens, thereby strengthening our defense against such adversaries.© 2024. The Author(s).