Utilizing TAPBPR to promote exogenous peptide loading onto cell surface MHC I molecules.
dc.contributor.author | Ilca, F Tudor | |
dc.contributor.author | Neerincx, Andreas | |
dc.contributor.author | Wills, Mark R | |
dc.contributor.author | de la Roche, Maike | |
dc.contributor.author | Boyle, Louise H | |
dc.date.accessioned | 2018-09-21T15:22:48Z | |
dc.date.available | 2018-09-21T15:22:48Z | |
dc.date.issued | 2018-10-02 | |
dc.identifier.issn | 0027-8424 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/280659 | |
dc.description.abstract | The 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.medium | Print-Electronic | |
dc.language | eng | |
dc.publisher | Proceedings of the National Academy of Sciences | |
dc.subject | T-Lymphocytes | |
dc.subject | Hela Cells | |
dc.subject | Animals | |
dc.subject | Mice, Knockout | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Peptides | |
dc.subject | Immunoglobulins | |
dc.subject | Membrane Proteins | |
dc.subject | Receptors, Antigen, T-Cell | |
dc.subject | Histocompatibility Antigens Class I | |
dc.subject | Immunity, Cellular | |
dc.subject | Antigen Presentation | |
dc.subject | Interferon-gamma | |
dc.subject | MCF-7 Cells | |
dc.title | Utilizing TAPBPR to promote exogenous peptide loading onto cell surface MHC I molecules. | |
dc.type | Article | |
prism.endingPage | E9361 | |
prism.issueIdentifier | 40 | |
prism.publicationDate | 2018 | |
prism.publicationName | Proc Natl Acad Sci U S A | |
prism.startingPage | E9353 | |
prism.volume | 115 | |
dc.identifier.doi | 10.17863/CAM.28025 | |
dcterms.dateAccepted | 2018-08-13 | |
rioxxterms.versionofrecord | 10.1073/pnas.1809465115 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2018-10 | |
dc.contributor.orcid | Ilca, F Tudor [0000-0002-6582-8007] | |
dc.contributor.orcid | Neerincx, Andreas [0000-0002-6902-5383] | |
dc.contributor.orcid | Wills, Mark R [0000-0001-8548-5729] | |
dc.contributor.orcid | de la Roche, Maike [0000-0002-0558-4119] | |
dc.contributor.orcid | Boyle, Louise H [0000-0002-3105-6555] | |
dc.identifier.eissn | 1091-6490 | |
rioxxterms.type | Journal Article/Review | |
pubs.funder-project-id | Wellcome Trust (104647/Z/14/Z) | |
pubs.funder-project-id | Cancer Research UK (C14303/A17197) | |
pubs.funder-project-id | Medical Research Council (MR/K021087/1) | |
pubs.funder-project-id | Medical Research Council (MR/S00081X/1) | |
pubs.funder-project-id | Wellcome Trust (107609/Z/15/Z) | |
cam.issuedOnline | 2018-09-13 | |
rioxxterms.freetoread.startdate | 2019-03-13 |
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