After TCR stimulation, two signaling pathways are induced via 3,4,5-triphosphate (IP3) and diacylglycerol (DAG)

After TCR stimulation, two signaling pathways are induced via 3,4,5-triphosphate (IP3) and diacylglycerol (DAG). The IP3-dependent pathway leads to Ca2+ release into the cytosol, activating NF-AT. The DAG-dependent pathway activates PKCθ and induces an oxidative signal via Complex I and III of the mitochondrial electron transport chain (ETC). Additionally, the MAPK signaling pathway is induced via PKCθ. The oxidative signal originating from mitochondrial ETC amplifies the MAPK signaling pathway and activates the redox-sensitive transcription factors AP1, NF-κB, and Nrf2. AP1 and NF-κB, together with NF-AT, create the minimal requirement for T cell activation. Conversely, Nrf2, by inducing antioxidant proteins, contributes to the control and potential termination of the oxidative signal. The figure was created with BioRender.com Oxidative signals in T cells are essential for the initiation of a T cell immune response. Several publications and data have addressed the induction of oxidative signals by TCR stimulation and the mechanisms by which these signals are generated. However, the role of co-stimulation in oxidative signaling is not well understood. This represents a knowledge gap that urgently needs to be investigated in detail

Publication

Unraveling the Role of Reactive Oxygen Species in T Lymphocyte Signaling (2024) Karsten Gülow, et al. Int J Mol Sci. 2024 Jun;25(11). Figure: F7. Homo sapiens

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