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dc.contributor.authorTregaskes, Cliveen
dc.contributor.authorHarrison, Michaelen
dc.contributor.authorSowa, Anna Ken
dc.contributor.authorHateren, Andy vanen
dc.contributor.authorHunt, Lawrence Gen
dc.contributor.authorVainio, Ollien
dc.contributor.authorKaufman, Jimen
dc.date.accessioned2015-12-17T16:02:41Z
dc.date.available2015-12-17T16:02:41Z
dc.date.issued2015-12-22en
dc.identifier.citationTregaskes et al. Proceedings of the National Academy of Sciences (2015) Vol. 113 no. 3, pp. 692–697. doi:10.1073/pnas.1511859113en
dc.identifier.issn0027-8424
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/253011
dc.description.abstractThe chicken major histocompatibility complex (MHC) has strong genetic associations with resistance and susceptibility to certain infectious pathogens. The cell surface expression level of MHC class I molecules varies as much as ten-fold between chicken haplotypes, and is inversely correlated with diversity of peptide repertoire and with resistance to Marek's disease caused by an oncogenic herpesvirus. Here we show that the average thermostability of class I molecules isolated from cells also varies, being higher for high expressing MHC haplotypes. However, we find roughly the same amount of class I protein synthesized by high and low expressing MHC haplotypes, with movement to the cell surface responsible for the difference in expression. Previous data shows that chicken TAP genes have high allelic polymorphism, with peptide translocation specific for each MHC haplotype. Here we use assembly assays with peptide libraries to show that high expressing B15 class I molecules can bind a much wider variety of peptides than are found on the cell surface, with the B15 TAPs restricting the peptides available. In contrast, the translocation specificity of TAPs from the low expressing B21 haplotype is even more permissive than the promiscuous binding shown by the dominantly-expressed class I molecule. B15/B21 heterozygote cells show much greater expression of B15 class I molecules than B15/B15 homozygote cells, presumably due to receiving additional peptides from the B21 TAPs. Thus, chicken MHC haplotypes vary in several correlated attributes, with the most obvious candidate linking all these properties being molecular interactions within the peptide-loading complex (PLC).
dc.description.sponsorshipThis work was originally supported by core funding to the Basel Institute for Immunology (which was founded and supported by F. Hoffmann-La Roche & Co. Ltd., CH-4005 Basel, Switzerland), then by core funding to the Institute for Animal Health [now re-branded the Pirbright Institute, sponsored by the Biotechnology and Biological Sciences Research Council (BBSRC) of the UK] and finally by programme grant 089305 from the Wellcome Trust to JK.
dc.languageEnglishen
dc.language.isoenen
dc.publisherNational Academy of Sciences
dc.subjectABC transporteren
dc.subjectrestrictiveen
dc.subjectpermissiveen
dc.subjectheterozogous advantageen
dc.subjectoverdominanceen
dc.titleSurface expression, peptide repertoire and thermostability of chicken class I molecules correlate with peptide transporter specificityen
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available from PNAS via http://dx.doi.org/10.1073/pnas.1511859113en
prism.endingPage697
prism.publicationDate2015en
prism.publicationNameProceedings of the National Academy of Sciencesen
prism.startingPage692
prism.volume113en
dc.rioxxterms.funderBBSRC
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.projectid089305
rioxxterms.versionofrecord10.1073/pnas.1511859113en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-12-22en
dc.contributor.orcidTregaskes, Clive [0000-0002-5750-0853]
dc.contributor.orcidKaufman, Jim [0000-0002-7216-8422]
dc.identifier.eissn1091-6490
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (089305/Z/09/Z)
rioxxterms.freetoread.startdate2016-06-22


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