Previously our lab has shown that co-stimulation of human T cells through different co-stimulatory molecules tune differentiation to different phenotypes. An open question is where in the signaling pathways induced by the co-stimulation do differences occur that contribute to outcome of differentiation. In this project, we investigate the early signaling process by comparing events that follow engagement of CD45 alone or in association with a co-stimulatory molecule: CD28. CD45 plays a crucial role to initiate T cell signaling by dephosphorylating a negatively regulatory tyrosine residue in Src family kinases such as Lck. First, we observed that engagement of CD45 alone induced signaling in T cells. We observed that TCR/CD3 stimulation with CD45 promoted prolonged Lck association with TCR/CD3 complex and Lck remained associated during TCR/CD3 + CD28 + CD45 stimulation as well. We concluded that Lck association is dependent on TCR/CD3 and CD45 engagement. Hence, CD45 altered early signaling events in T cells.

中文翻译：

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CD45的参与改变了通过TCR + CD28共刺激的人类T细胞中的早期信号传导事件。

以前，我们的实验室表明，通过不同的共刺激分子对人类T细胞的共刺激可将分化调节为不同的表型。一个悬而未决的问题是，在共刺激诱导的信号传导路径中的哪些位置会发生导致分化结果的差异。在这个项目中，我们通过比较单独参与CD45或与共刺激分子CD28结合后的事件来研究早期信号传导过程。CD45通过使Src家族激酶（如Lck）中的负调节酪氨酸残基去磷酸化，在启动T细胞信号传导中起关键作用。首先，我们观察到单独的CD45参与会诱导T细胞中的信号传导。我们观察到，用CD45刺激TCR / CD3可以延长Lck与TCR / CD3复合体的缔合，并且在TCR / CD3 + CD28 + CD45刺激过程中Lck仍保持缔合。我们得出的结论是，Lck关联取决于TCR / CD3和CD45的参与。因此，CD45改变了T细胞中的早期信号传导事件。