The field of immunology has long been fascinated by the intricate mechanisms of early intracellular signaling in T lymphocytes, particularly following antigen recognition by the T Cell Receptor (TCR). This signaling cascade is crucial for the development, activation, and differentiation of T cells, with early signals involving key phosphorylation events mediated by tyrosine kinases such as Lck and ZAP70. These kinases sequentially activate and phosphorylate the transmembrane adaptor LAT, forming a signaling hub that ultimately leads to T-cell activation. Despite significant advancements in understanding these early signaling events, there remains a substantial gap in knowledge regarding the molecular mechanisms that negatively regulate these signals. Such negative regulation is critical, as its malfunction can lead to pathologies, including autoimmune disorders. Furthermore, a comprehensive understanding of TCR signaling is essential for the development of innovative therapeutic strategies, such as CAR-T cell therapies, underscoring the need for continued research in this area.

This research topic aims to explore the latest advances in early intracellular signaling associated with the TCR, focusing on both the activation and negative regulation mechanisms. It seeks to address the dual roles of elements within the TCR signaling cascade, such as Lck, ZAP70, CD45 phosphatase, LAT, and NTAL adaptors, which participate in negative feedback loops. By investigating these mechanisms, the research aims to elucidate how T cells distinguish between foreign and self-antigens, the activation and differentiation of naive T cells, and the maintenance of immune homeostasis. Ultimately, this research will contribute to a deeper understanding of TCR signaling self-regulation, with implications for immunology and the development of therapies for immune-based diseases.

To gather further insights into the mechanisms of early intracellular signaling in T lymphocytes, we welcome articles addressing, but not limited to, the following themes:
- Role of tyrosine and threonine/serine kinases and phosphatases as regulators of TCR signaling.
- Rapid endocytic recycling of TCR and associated signaling adaptors as a regulatory hub in TCR signaling.
- Costimulatory and coinhibitory receptors in early intracellular signaling coupled to the TCR/CD3 signaling cassette.
- Relevance of negative regulation of the TCR signaling cassette for thymic maturation: TCR signaling during thymic positive and negative selection.
- Perturbations of regulatory mechanisms of TCR signaling and pathological implications, including new therapeutic approaches for immune-based pathologies.
- Harnessing the TCR signaling machinery for efficient CAR-T cell therapies.
- Differences in TCR signaling pathways between effector and regulatory T cells.
- Membrane dynamics and nanoscale organization of TCR-associated molecules in the regulation of TCR signaling.

We welcome authors to submit Original Research, Review and Case Reports focusing on the mechanisms of early intracellular signaling in T lymphocytes.

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Frontiers in Immunology

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