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dc.contributor.authorIlca, F Tudor
dc.contributor.authorNeerincx, Andreas
dc.contributor.authorWills, Mark
dc.contributor.authorde la Roche, Maike
dc.contributor.authorBoyle, Louise
dc.date.accessioned2018-09-21T15:22:48Z
dc.date.available2018-09-21T15:22:48Z
dc.date.issued2018-10-02
dc.identifier.issn0027-8424
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280659
dc.description.abstractThe repertoire of peptides displayed at the cell surface by MHC I molecules is shaped by two intracellular peptide editors, tapasin and TAPBPR. While cell-free assays have proven extremely useful in identifying the function of both of these proteins, here we explored whether a more physiological system could be developed to assess TAPBPR-mediated peptide editing on MHC I. We reveal that membrane-associated TAPBPR targeted to the plasma membrane retains its ability to function as a peptide editor and efficiently catalyzes peptide exchange on surface-expressed MHC I molecules. Additionally, we show that soluble TAPBPR, consisting of the luminal domain alone, added to intact cells, also functions as an effective peptide editor on surface MHC I molecules. Thus, we have established two systems in which TAPBPR-mediated peptide exchange on MHC class I can be interrogated. Furthermore, we could use both plasma membrane-targeted and exogenous soluble TAPBPR to display immunogenic peptides on surface MHC I molecules and consequently induce T cell receptor engagement, IFN-γ secretion, and T cell-mediated killing of target cells. Thus, we have developed an efficient way to by-pass the natural antigen presentation pathway of cells and load immunogenic peptides of choice onto cells. Our findings highlight a potential therapeutic use for TAPBPR in increasing the immunogenicity of tumors in the future.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherProceedings of the National Academy of Sciences
dc.subjectT-Lymphocytes
dc.subjectHela Cells
dc.subjectAnimals
dc.subjectMice, Knockout
dc.subjectHumans
dc.subjectMice
dc.subjectPeptides
dc.subjectImmunoglobulins
dc.subjectMembrane Proteins
dc.subjectReceptors, Antigen, T-Cell
dc.subjectHistocompatibility Antigens Class I
dc.subjectImmunity, Cellular
dc.subjectAntigen Presentation
dc.subjectInterferon-gamma
dc.subjectMCF-7 Cells
dc.titleUtilizing TAPBPR to promote exogenous peptide loading onto cell surface MHC I molecules.
dc.typeArticle
prism.endingPageE9361
prism.issueIdentifier40
prism.publicationDate2018
prism.publicationNameProc Natl Acad Sci U S A
prism.startingPageE9353
prism.volume115
dc.identifier.doi10.17863/CAM.28025
dcterms.dateAccepted2018-08-13
rioxxterms.versionofrecord10.1073/pnas.1809465115
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-10
dc.contributor.orcidIlca, F Tudor [0000-0002-6582-8007]
dc.contributor.orcidNeerincx, Andreas [0000-0002-6902-5383]
dc.contributor.orcidWills, Mark [0000-0001-8548-5729]
dc.contributor.orcidde la Roche, Maike [0000-0002-0558-4119]
dc.contributor.orcidBoyle, Louise [0000-0002-3105-6555]
dc.identifier.eissn1091-6490
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (104647/Z/14/Z)
pubs.funder-project-idCancer Research UK (C14303/A17197)
pubs.funder-project-idMedical Research Council (MR/K021087/1)
pubs.funder-project-idMedical Research Council (MR/S00081X/1)
cam.issuedOnline2018-09-13
rioxxterms.freetoread.startdate2019-03-13


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