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Nat Immunol. 2018 Aug;19(8):849-858. doi: 10.1038/s41590-018-0160-9. Epub 2018 Jul 16.

T cell cytolytic capacity is independent of initial stimulation strength.

Author information

1
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
2
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
3
Department of Haematology, Wellcome - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
4
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK. john.marioni@cruk.cam.ac.uk.
5
European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Cambridge, UK. john.marioni@cruk.cam.ac.uk.
6
Wellcome Sanger Institute, Cambridge, UK. john.marioni@cruk.cam.ac.uk.
7
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK. gg305@cam.ac.uk.

Abstract

How cells respond to myriad stimuli with finite signaling machinery is central to immunology. In naive T cells, the inherent effect of ligand strength on activation pathways and endpoints has remained controversial, confounded by environmental fluctuations and intercellular variability within populations. Here we studied how ligand potency affected the activation of CD8+ T cells in vitro, through the use of genome-wide RNA, multi-dimensional protein and functional measurements in single cells. Our data revealed that strong ligands drove more efficient and uniform activation than did weak ligands, but all activated cells were fully cytolytic. Notably, activation followed the same transcriptional pathways regardless of ligand potency. Thus, stimulation strength did not intrinsically dictate the T cell-activation route or phenotype; instead, it controlled how rapidly and simultaneously the cells initiated activation, allowing limited machinery to elicit wide-ranging responses.

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PMID:
30013148
PMCID:
PMC6300116
DOI:
10.1038/s41590-018-0160-9
[Indexed for MEDLINE]
Free PMC Article

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