About this Research Topic
Antigen recognition by the T Cell receptor (TCR) triggers a signaling cascade that controls the development, activation, and terminal differentiation of T cells. Early TCR signals include phosphorylation events in which the tyrosine kinases Lck and ZAP70 are involved. The sequential activation of these kinases leads to the phosphorylation of tyrosine residues in the transmembrane adaptor LAT, which constitutes a signaling hub for the generation of a signalosome, finally resulting in T-cell activation. Although there has been a huge increase in knowledge on early intracellular signaling in recent years, much less is known about the molecular mechanisms negatively regulating early TCR intracellular signals, which can lead to malfunction that triggers pathologies. In addition, a thorough understanding of TCR signaling can have a decisive impact on the design of new therapeutic approaches, such as the use of CAR-T cells. This research topic aims to address the latest advances in the field of early intracellular signaling associated with TCR.
Some reports have revealed that some elements of the TCR signaling cascade have a dual role, activator and negative regulator. Lck and ZAP70 kinases, CD45 phosphatase, LAT, and NTAL adaptors have been shown to participate in negative feedback loops. This has consequences in the way T cells discriminate foreign from self-antigens, how naive T cells are activated and differentiate into effector and memory cells, and also in immune homeostasis. All these events are of critical relevance for T cell development and efficient immune responses, allowing the avoidance of autoimmune disorders. A deeper understanding of how the TCR signaling cassette is self-regulated is necessary, not only for the benefit of immunology but also to lay the foundations for future advances in therapies for immune-based diseases.
The aim of the current Research Topic is to collect recent and novel research trends in the field of early intracellular signaling coupled to the TCR/CD3 complex. Areas to be covered in this Research Topic may include, but are not limited to:
• 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.
Some reports have revealed that some elements of the TCR signaling cascade have a dual role, activator and negative regulator. Lck and ZAP70 kinases, CD45 phosphatase, LAT, and NTAL adaptors have been shown to participate in negative feedback loops. This has consequences in the way T cells discriminate foreign from self-antigens, how naive T cells are activated and differentiate into effector and memory cells, and also in immune homeostasis. All these events are of critical relevance for T cell development and efficient immune responses, allowing the avoidance of autoimmune disorders. A deeper understanding of how the TCR signaling cassette is self-regulated is necessary, not only for the benefit of immunology but also to lay the foundations for future advances in therapies for immune-based diseases.
The aim of the current Research Topic is to collect recent and novel research trends in the field of early intracellular signaling coupled to the TCR/CD3 complex. Areas to be covered in this Research Topic may include, but are not limited to:
• 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.
Keywords: TCR, T lymphocytes, thymic development, CAR-T signaling, adaptor proteins, T cell activation
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
