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T cell cytolytic capacity is independent of initial stimulation strength.

Accepted version
Peer-reviewed

Type

Article

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Authors

Richard, Arianne C 
Göttgens, Berthold 

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.

Description

Keywords

Animals, CD8-Positive T-Lymphocytes, Cell Line, Cytotoxicity, Immunologic, Genome, Lymphocyte Activation, Mice, Mice, Inbred C57BL, RNA, Receptors, Antigen, T-Cell, alpha-beta, Signal Transduction, Single-Cell Analysis

Journal Title

Nat Immunol

Conference Name

Journal ISSN

1529-2908
1529-2916

Volume Title

19

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (103930/Z/14/Z)
Medical Research Council (MR/P014178/1)
Leukaemia & Lymphoma Research (12029)
Cancer Research UK (21762)
Cancer Research UK (C14303/A17197)
Medical Research Council (MC_PC_12009)
Wellcome Trust (100140/Z/12/Z)
Medical Research Council (MR/M008975/1)