ArticleImmunity2009
Kinetics of early T cell receptor signaling regulate the pathway of lytic granule delivery to the secretory domain.
Article in Immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed.
- CD4Trends in cancer · 2024Review
- Single-cell topographical profiling of the immune synapse reveals a biomechanical signature of cytotoxicity.Science immunology · 2024Article
- Human PLCG2 haploinsufficiency results in a novel natural killer cell immunodeficiency.The Journal of allergy and clinical immunology · 2024Article
- Cytosolic protein translation regulates cell asymmetry and function in early TCR activation of human CD8Frontiers in immunology · 2024Article
- T-cell response to checkpoint blockade immunotherapies: from fundamental mechanisms to treatment signatures.Essays in biochemistry · 2023Review
- Factors contributing to the potency of CD8Trends in immunology · 2023Review
- Human natural killer cells: Form, function, and development.The Journal of allergy and clinical immunology · 2023Review
- Adenosine A2a Receptor Antagonism Restores Additive Cytotoxicity by Cytotoxic T Cells in Metabolically Perturbed Tumors.Cancer immunology research · 2022Article
- Joining Forces for Cancer Treatment: From "TCR versus CAR" to "TCR and CAR".International journal of molecular sciences · 2022Review
- Immune mobilising T cell receptors redirect polyclonal CD8Scientific reports · 2022Article
- The immune synapses reveal aberrant functions of CD8 T cells during chronic HIV infection.Nature communications · 2022Article
- Mechanically active integrins target lytic secretion at the immune synapse to facilitate cellular cytotoxicity.Nature communications · 2022Article
- Cytotoxic T Lymphocyte Activation Signals Modulate Cytoskeletal Dynamics and Mechanical Force Generation.Frontiers in immunology · 2022Article
- Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.Frontiers in immunology · 2022Review
- Staggered starts in the race to T cell activation.Trends in immunology · 2021Review
- Signal strength controls the rate of polarization within CTLs during killing.The Journal of cell biology · 2021Article
- Review
- Dynamic Microtubule Arrays in Leukocytes and Their Role in Cell Migration and Immune Synapse Formation.Frontiers in cell and developmental biology · 2021Review
- Vitamin C, From Supplement to Treatment: A Re-Emerging Adjunct for Cancer Immunotherapy?Frontiers in immunology · 2021Review
- Design and Implementation of NK Cell-Based Immunotherapy to Overcome the Solid Tumor Microenvironment.Cancers · 2020Review
24 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
Cytolytic granules mediate killing of virus-infected cells by cytotoxic T lymphocytes. We show here that the granules can take long or short paths to the secretory domain. Both paths utilized the same intracellular molecular events, which have different spatial and temporal arrangements and are regulated by the kinetics of Ca(2+)-mediated signaling. Rapid signaling caused swift granule concentration near the microtubule-organizing center (MTOC) and subsequent delivery by the polarized MTOC directly to the secretory domain-the shortest path. Indolent signaling led to late recruitment of granules that moved along microtubules to the periphery of the synapse and then moved tangentially to fuse at the outer edge of the secretory domain-a longer path. The short pathway is associated with faster granule release and more efficient killing than the long pathway. Thus, the kinetics of early signaling regulates the quality of the T cell cytolytic response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.