Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands.
Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, 75013 Paris, France.
Cell Rep. 2022 Jun 28;39(13):111006. doi: 10.1016/j.celrep.2022.111006.
T cells depend on the phosphatase CD45 to initiate T cell receptor signaling. Although the critical role of CD45 in T cells is established, the mechanisms controlling function and localization in the membrane are not well understood. Moreover, the regulation of specific CD45 isoforms in T cell signaling remains unresolved. By using unbiased mass spectrometry, we identify the tetraspanin CD53 as a partner of CD45 and show that CD53 controls CD45 function and T cell activation. CD53-negative T cells (Cd53) exhibit substantial proliferation defects, and Cd53 mice show impaired tumor rejection and reduced IFNγ-producing T cells compared with wild-type mice. Investigation into the mechanism reveals that CD53 is required for CD45RO expression and mobility. In addition, CD53 is shown to stabilize CD45 on the membrane and is required for optimal phosphatase activity and subsequent Lck activation. Together, our findings reveal CD53 as a regulator of CD45 activity required for T cell immunity.
T 细胞依赖磷酸酶 CD45 来启动 T 细胞受体信号转导。虽然 CD45 在 T 细胞中的关键作用已经确立，但控制其功能和在膜中定位的机制尚不清楚。此外，T 细胞信号转导中特定 CD45 同工型的调节仍未解决。通过使用无偏质谱分析，我们确定四跨膜蛋白 CD53 是 CD45 的一个伴侣，并表明 CD53 控制 CD45 的功能和 T 细胞的激活。缺乏 CD53 的 T 细胞（Cd53）表现出明显的增殖缺陷，与野生型小鼠相比，Cd53 小鼠显示出肿瘤排斥受损和 IFNγ产生 T 细胞减少。对机制的研究表明，CD53 是 CD45RO 表达和迁移所必需的。此外，CD53 被证明可以稳定细胞膜上的 CD45，并需要最佳的磷酸酶活性和随后的 Lck 激活。总之，我们的研究结果揭示了 CD53 作为 T 细胞免疫所必需的 CD45 活性调节剂。
