Engagement of CD45 alters early signaling events in human T cells co-stimulated through TCR + CD28.

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.

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