Signal strength controls the rate of polarization within CTLs during killing

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 g...

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Veröffentlicht in:The Journal of cell biology 2021-10, Vol.220 (10)
Hauptverfasser: Frazer, Gordon L., Gawden-Bone, Christian M., Dieckmann, Nele M.G., Asano, Yukako, Griffiths, Gillian M.
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container_issue 10
container_start_page
container_title The Journal of cell biology
container_volume 220
creator Frazer, Gordon L.
Gawden-Bone, Christian M.
Dieckmann, Nele M.G.
Asano, Yukako
Griffiths, Gillian M.
description 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.
doi_str_mv 10.1083/jcb.202104093
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subjects Amino acid sequence
Amino acids
Calcium ions
Cell recognition
Cytotoxicity
Dwell time
Effector cells
Granular materials
Immune response
Immune system
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Organelles
Peptides
Polarization
Signal strength
T cell receptors
Target recognition
title Signal strength controls the rate of polarization within CTLs during killing
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