Show simple item record

dc.contributor.authorLee, Jeansun
dc.contributor.authorDieckmann, Nele MG
dc.contributor.authorEdgar, James R
dc.contributor.authorGriffiths, Gillian M
dc.contributor.authorSiegel, Richard M
dc.date.accessioned2018-06-04T12:39:16Z
dc.date.available2018-06-04T12:39:16Z
dc.date.issued2018-06
dc.identifier.issn2050-4527
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/276537
dc.description.abstractINTRODUCTION: T cell and NK cell cytotoxicity can be mediated via the perforin/granzyme system and Fas Ligand (FasL, CD178). FasL is synthesized as a type II transmembrane protein that binds its cognate receptor Fas (CD95). Membrane-bound FasL is expressed on the plasma membrane of activated lymphocytes and is the main form of FasL with cytotoxic activity, but whether FasL is delivered to the immune synapse along with granzyme and perforin-containing granules is unclear. METHODS: We stably expressed FasL-fluorescent fusion proteins into human NK cells and examined the localization of FasL relative to other intracellular markers by confocal and immunoelectron microscopy, and examined the trafficking of FasL during formation of immune synapses with HLA-deficient B cells. RESULTS: FasL co-localized with CD63 more strongly than perforin or Lamp1+ in cytolytic granules. Electron microscopy revealed that FasL is enriched on intraluminal vesicles (ILVs) adjacent to the dense-core within cytolytic granules. In NK cells forming immune synapses with HLA-deficient B cells, a portion of FasL-containing granules re-localize toward the immune synapse, while a distinct pool of FasL remains at the distal pole of the cell. CONCLUSIONS: Localization of FasL to intra-luminal vesicles within cytolytic granules facilitates FasL trafficking to immune synapses and cytotoxic function in NK cells.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherWiley
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectB-Lymphocytes
dc.subjectKiller Cells, Natural
dc.subjectCell Line
dc.subjectCytoplasmic Granules
dc.subjectHumans
dc.subjectHLA Antigens
dc.subjectMicroscopy, Electron
dc.subjectCell Culture Techniques
dc.subjectGranzymes
dc.subjectFas Ligand Protein
dc.subjectPerforin
dc.subjectImmunological Synapses
dc.subjectTetraspanin 30
dc.titleFas Ligand localizes to intraluminal vesicles within NK cell cytolytic granules and is enriched at the immune synapse.
dc.typeArticle
prism.endingPage321
prism.issueIdentifier2
prism.publicationDate2018
prism.publicationNameImmun Inflamm Dis
prism.startingPage312
prism.volume6
dc.identifier.doi10.17863/CAM.23837
dcterms.dateAccepted2018-02-06
rioxxterms.versionofrecord10.1002/iid3.219
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-06
dc.contributor.orcidSiegel, Richard M [0000-0001-5953-9893]
dc.identifier.eissn2050-4527
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idWellcome Trust (103930/Z/14/Z)
cam.issuedOnline2018-04-11
cam.orpheus.successThu Jan 30 12:58:59 GMT 2020 - The item has an open VoR version.
rioxxterms.freetoread.startdate2100-01-01


Files in this item

Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International