ArticleThe Journal of cell biology2021
Signal strength controls the rate of polarization within CTLs during killing.
Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed.
- Tumor cell spheroid-induced suppression of primary human cytotoxic T cells as a scalableImmunotherapy advances · 2025Article
- Smart lattice light-sheet microscopy for imaging rare and complex cellular events.Nature methods · 2024Article
- T-cell response to checkpoint blockade immunotherapies: from fundamental mechanisms to treatment signatures.Essays in biochemistry · 2023Review
- Temperature sensitive liposome based cancer nanomedicine enables tumour lymph node immune microenvironment remodelling.Nature communications · 2023Article
- Modeling cell-mediated immunity in human type 1 diabetes by engineering autoreactive CD8Frontiers in immunology · 2023Article
- Phenotyping polarization dynamics of immune cells using a lipid droplet-cell pairing microfluidic platform.Cell reports methods · 2022Article
- Divide and Conquer: Phenotypic and Temporal Heterogeneity Within CD8Frontiers in immunology · 2022Review
- Review
- The Era of Cytotoxic CD4 T Cells.Frontiers in immunology · 2022Review
- The Expanding Arsenal of Cytotoxic T Cells.Frontiers in immunology · 2022Review
- Staggered starts in the race to T cell activation.Trends in immunology · 2021Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Cytotoxic T lymphocytes (CTLs) are key effector cells in the immune response against viruses and cancers, killing targets with high precision. Target cell recognition by CTL triggers rapid polarization of intracellular organelles toward the synapse formed with the target cell, delivering cytolytic granules to the immune synapse. Single amino acid changes within peptides binding MHC class I (pMHCs) are sufficient to modulate the degree of killing, but exactly how this impacts the choreography of centrosome polarization and granule delivery to the target cell remains poorly characterized. Here we use 4D imaging and find that the pathways orchestrating killing within CTL are conserved irrespective of the signal strength. However, the rate of initiation along these pathways varies with signal strength. We find that increased strength of signal leads to an increased proportion of CTLs with prolonged dwell times, initial Ca2+ fluxes, centrosome docking, and granule polarization. Hence, TCR signal strength modulates the rate but not organization of effector CTL responses.
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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.