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dc.contributor.authorRichard, Arianneen
dc.contributor.authorLun, Aaronen
dc.contributor.authorLau, Winnieen
dc.contributor.authorGottgens, Bertholden
dc.contributor.authorMarioni, Johnen
dc.contributor.authorGriffiths, Gillianen
dc.date.accessioned2018-09-08T06:29:14Z
dc.date.available2018-09-08T06:29:14Z
dc.date.issued2018-08en
dc.identifier.issn1529-2908
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279751
dc.description.abstractHow cells respond to a myriad of stimuli with finite signaling machinery is central to immunology. In naive T cells, the inherent effect of ligand strength on activation pathways and endpoints remains controversial, confounded by environmental fluctuations and intercellular variability within populations. Here, we study how ligand potency affects CD8+ T cell activation in vitro using genome-wide RNA, multi-dimensional protein and functional measurements in single cells. Our data reveal that strong ligands drive more efficient and uniform activation than weak ligands, but all activated cells are fully cytolytic. Importantly, activation follows the same transcriptional pathways, regardless of ligand potency. Thus, stimulation strength does not intrinsically dictate T cell activation route or phenotype; instead it controls how rapidly and simultaneously cells initiate activation, allowing limited machinery to elicit wide-ranging responses.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherSpringer Nature
dc.subjectCD8-Positive T-Lymphocytesen
dc.subjectCell Lineen
dc.subjectAnimalsen
dc.subjectMice, Inbred C57BLen
dc.subjectMiceen
dc.subjectReceptors, Antigen, T-Cell, alpha-betaen
dc.subjectRNAen
dc.subjectLymphocyte Activationen
dc.subjectSignal Transductionen
dc.subjectCytotoxicity, Immunologicen
dc.subjectGenomeen
dc.subjectSingle-Cell Analysisen
dc.titleT cell cytolytic capacity is independent of initial stimulation strength.en
dc.typeArticle
prism.endingPage858
prism.issueIdentifier8en
prism.publicationDate2018en
prism.publicationNameNature immunologyen
prism.startingPage849
prism.volume19en
dc.identifier.doi10.17863/CAM.27121
dcterms.dateAccepted2018-05-31en
rioxxterms.versionofrecord10.1038/s41590-018-0160-9en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-08en
dc.contributor.orcidLun, Aaron [0000-0002-3564-4813]
dc.contributor.orcidLau, Winnie [0000-0003-1209-1854]
dc.contributor.orcidGöttgens, Berthold [0000-0001-6302-5705]
dc.contributor.orcidMarioni, John [0000-0001-9092-0852]
dc.contributor.orcidGriffiths, Gillian [0000-0003-0434-5842]
dc.identifier.eissn1529-2916
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWELLCOME TRUST (103930/Z/14/Z)
pubs.funder-project-idMRC (MR/P014178/1)
pubs.funder-project-idLeukaemia & Lymphoma Research (12029)
pubs.funder-project-idCancer Research UK (21762)
pubs.funder-project-idCancer Research UK (C14303/A17197)
pubs.funder-project-idMRC (MC_PC_12009)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (MR/M008975/1)
rioxxterms.freetoread.startdate2019-01-16


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