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dc.date.accessioned2018-05-28T12:31:00Z
dc.date.available2018-05-28T12:31:00Z
dc.date.created2017-11-22T13:18:47Z
dc.date.issued2017
dc.identifier.citationGunnarsen, Kristin Støen Høydahl, Lene Støkken Risnes, Louise Fremgaard Dahal-Koirala, Shiva Neumann, Ralf Stefan Bergseng, Elin Frigstad, Terje Frick, Rahel du Pré, Marie Fleur Dalhus, Bjørn Lundin, Knut Erik Aslaksen Qiao, Shuo Wang Sollid, Ludvig Magne Sandlie, Inger Løset, Geir Åge . A TCRα framework–centered codon shapes a biased T cell repertoire through direct MHC and CDR3β interactions. JCI Insight. 2017
dc.identifier.urihttp://hdl.handle.net/10852/61753
dc.description.abstractSelection of biased T cell receptor (TCR) repertoires across individuals is seen in both infectious diseases and autoimmunity, but the underlying molecular basis leading to these shared repertoires remains unclear. Celiac disease (CD) occurs primarily in HLA-DQ2.5+ individuals and is characterized by a CD4+ T cell response against gluten epitopes dominated by DQ2.5-glia-α1a and DQ2.5-glia-α2. The DQ2.5-glia-α2 response recruits a highly biased TCR repertoire composed of TRAV26-1 paired with TRBV7-2 harboring a semipublic CDR3β loop. We aimed to unravel the molecular basis for this signature. By variable gene segment exchange, directed mutagenesis, and cellular T cell activation studies, we found that TRBV7-3 can substitute for TRBV7-2, as both can contain the canonical CDR3β loop. Furthermore, we identified a pivotal germline-encoded MHC recognition motif centered on framework residue Y40 in TRAV26-1 engaging both DQB1*02 and the canonical CDR3β. This allowed prediction of expanded DQ2.5-glia-α2–reactive TCR repertoires, which were confirmed by single-cell sorting and TCR sequencing from CD patient samples. Our data refine our understanding of how HLA-dependent biased TCR repertoires are selected in the periphery due to germline-encoded residues. This research was originally published in JCI Insight. © 2018 American Society for Clinical Investigationen_US
dc.languageEN
dc.publisherAmerican Society for Clinical Investigation (ASCI)
dc.titleA TCRα framework–centered codon shapes a biased T cell repertoire through direct MHC and CDR3β interactionsen_US
dc.typeJournal articleen_US
dc.creator.authorGunnarsen, Kristin Støen
dc.creator.authorHøydahl, Lene Støkken
dc.creator.authorRisnes, Louise Fremgaard
dc.creator.authorDahal-Koirala, Shiva
dc.creator.authorNeumann, Ralf Stefan
dc.creator.authorBergseng, Elin
dc.creator.authorFrigstad, Terje
dc.creator.authorFrick, Rahel
dc.creator.authordu Pré, Marie Fleur
dc.creator.authorDalhus, Bjørn
dc.creator.authorLundin, Knut Erik Aslaksen
dc.creator.authorQiao, Shuo Wang
dc.creator.authorSollid, Ludvig Magne
dc.creator.authorSandlie, Inger
dc.creator.authorLøset, Geir Åge
cristin.unitcode185,53,2,11
cristin.unitnameSenter for immunregulering
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1517206
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=JCI Insight&rft.volume=&rft.spage=&rft.date=2017
dc.identifier.jtitleJCI Insight
dc.identifier.doihttp://dx.doi.org/10.1172/jci.insight.95193
dc.identifier.urnURN:NBN:no-64356
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn2379-3708
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/61753/1/Gunnarsen%2BKS%2Bet%2Bal%252C%2BJCI%2BInsight%252C%2B2017.pdf
dc.type.versionPublishedVersion
dc.relation.projectHSØ/2015095


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