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dc.contributor.authorIlca, F Tudor
dc.contributor.authorNeerincx, Andreas
dc.contributor.authorHermann, Clemens
dc.contributor.authorMarcu, Ana
dc.contributor.authorStevanović, Stefan
dc.contributor.authorDeane, Janet
dc.contributor.authorBoyle, Louise
dc.date.accessioned2018-12-20T00:30:36Z
dc.date.available2018-12-20T00:30:36Z
dc.date.issued2018-11-28
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287215
dc.description.abstractTapasin and TAPBPR are known to perform peptide editing on major histocompatibility complex class I (MHC I) molecules; however, the precise molecular mechanism(s) involved in this process remain largely enigmatic. Here, using immunopeptidomics in combination with novel cell-based assays that assess TAPBPR-mediated peptide exchange, we reveal a critical role for the K22-D35 loop of TAPBPR in mediating peptide exchange on MHC I. We identify a specific leucine within this loop that enables TAPBPR to facilitate peptide dissociation from MHC I. Moreover, we delineate the molecular features of the MHC I F pocket required for TAPBPR to promote peptide dissociation in a loop-dependent manner. These data reveal that chaperone-mediated peptide editing on MHC I can occur by different mechanisms dependent on the C-terminal residue that the MHC I accommodates in its F pocket and provide novel insights that may inform the therapeutic potential of TAPBPR manipulation to increase tumour immunogenicity.
dc.description.sponsorshipWellcome PhD studentship (109076/Z/15/A). Wellcome Senior Research Fellowship (104647/Z/14/Z) South African Medical Research Council Bosch-Forschungsstiftung. Royal Society University Research Fellowship (UF100371).
dc.format.mediumElectronic
dc.languageeng
dc.publishereLife Sciences Publications, Ltd
dc.subjectHela Cells
dc.subjectHumans
dc.subjectLeucine
dc.subjectPeptides
dc.subjectImmunoglobulins
dc.subjectMembrane Proteins
dc.subjectHistocompatibility Antigens Class I
dc.subjectHLA-A Antigens
dc.subjectAntigen Presentation
dc.subjectBinding Sites
dc.subjectAmino Acid Sequence
dc.subjectProtein Binding
dc.subjectMutation
dc.subjectMolecular Docking Simulation
dc.subjectProtein Domains
dc.titleTAPBPR mediates peptide dissociation from MHC class I using a leucine lever.
dc.typeArticle
prism.publicationDate2018
prism.publicationNameElife
prism.volume7
dc.identifier.doi10.17863/CAM.34522
dcterms.dateAccepted2018-11-28
rioxxterms.versionofrecord10.7554/eLife.40126
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-11-28
dc.contributor.orcidIlca, F Tudor [0000-0002-6582-8007]
dc.contributor.orcidNeerincx, Andreas [0000-0002-6902-5383]
dc.contributor.orcidHermann, Clemens [0000-0002-0009-9501]
dc.contributor.orcidMarcu, Ana [0000-0003-0808-8097]
dc.contributor.orcidStevanović, Stefan [0000-0003-1954-7762]
dc.contributor.orcidDeane, Janet [0000-0002-4863-0330]
dc.contributor.orcidBoyle, Louise [0000-0002-3105-6555]
dc.identifier.eissn2050-084X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (104647/Z/14/Z)
pubs.funder-project-idRoyal Society (UF150682)
pubs.funder-project-idWellcome Trust (109076/Z/15/Z)
cam.issuedOnline2018-11-28
rioxxterms.freetoread.startdate2019-11-28


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