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dc.contributor.authorPaul-Heng, Moumita
dc.contributor.authorLeong, Mario
dc.contributor.authorCunningham, Eithne
dc.contributor.authorBunker, Daniel L J
dc.contributor.authorBremner, Katherine
dc.contributor.authorWang, Zane
dc.contributor.authorWang, Chuanmin
dc.contributor.authorTay, Szun Szun
dc.contributor.authorMcGuffog, Claire
dc.contributor.authorLogan, Grant J
dc.contributor.authorAlexander, Ian E
dc.contributor.authorHu, Min
dc.contributor.authorAlexander, Stephen I
dc.contributor.authorSparwasser, Tim D
dc.contributor.authorBertolino, Patrick
dc.contributor.authorBowen, David G
dc.contributor.authorBishop, G Alex
dc.contributor.authorSharland, Alexandra
dc.date.accessioned2020-02-12T15:13:26Z
dc.date.available2020-02-12T15:13:26Z
dc.date.issued2018-08-09
dc.identifier.citationJCI Insight. 2018 Aug 9;3(15). pii: 97500. doi: 10.1172/jci.insight.97500. eCollection 2018 Aug 9.en_US
dc.identifier.issn2379-3708
dc.identifier.pmid30089715
dc.identifier.doi10.1172/jci.insight.97500
dc.identifier.urihttp://hdl.handle.net/10033/622131
dc.description.abstractAdeno-associated viral vector–mediated (AAV-mediated) expression of allogeneic major histocompatibility complex class I (MHC class I) in recipient liver induces donor-specific tolerance in mouse skin transplant models in which a class I allele (H-2Kb or H-2Kd) is mismatched between donor and recipient. Tolerance can be induced in mice primed by prior rejection of a donor-strain skin graft, as well as in naive recipients. Allogeneic MHC class I may be recognized by recipient T cells as an intact molecule (direct recognition) or may be processed and presented as an allogeneic peptide in the context of self-MHC (indirect recognition). The relative contributions of direct and indirect allorecognition to tolerance induction in this setting are unknown. Using hepatocyte-specific AAV vectors encoding WT allogeneic MHC class I molecules, or class I molecules containing a point mutation (D227K) that impedes direct recognition of intact allogeneic MHC class I by CD8+ T cells without hampering the presentation of processed peptides derived from allogeneic MHC class I, we show here that tolerance induction depends upon recognition of intact MHC class I. Indirect recognition alone yielded a modest prolongation of subsequent skin graft survival, attributable to the generation of CD4+ Tregs, but it was not sufficient to induce tolerance.en_US
dc.language.isoenen_US
dc.publisherNLM (Medline)en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectAntigen presentationen_US
dc.subjectGene therapyen_US
dc.subjectHepatologyen_US
dc.subjectToleranceen_US
dc.subjectTransplantationen_US
dc.titleDirect recognition of hepatocyte-expressed MHC class I alloantigens is required for tolerance induction.en_US
dc.typeArticleen_US
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalJCI Insighten_US
refterms.dateFOA2020-02-12T15:13:26Z
dc.source.journaltitleJCI insight


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