Direct recognition of hepatocyte-expressed MHC class I alloantigens is required for tolerance induction.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Paul-Heng, MoumitaLeong, Mario
Cunningham, Eithne
Bunker, Daniel L J
Bremner, Katherine
Wang, Zane
Wang, Chuanmin
Tay, Szun Szun
McGuffog, Claire
Logan, Grant J
Alexander, Ian E
Hu, Min
Alexander, Stephen I
Sparwasser, Tim D
Bertolino, Patrick
Bowen, David G
Bishop, G Alex
Sharland, Alexandra
Issue Date
2018-08-09
Metadata
Show full item recordAbstract
Adeno-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.Citation
JCI Insight. 2018 Aug 9;3(15). pii: 97500. doi: 10.1172/jci.insight.97500. eCollection 2018 Aug 9.Affiliation
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.Publisher
NLM (Medline)Journal
JCI InsightPubMed ID
30089715Type
ArticleLanguage
enISSN
2379-3708ae974a485f413a2113503eed53cd6c53
10.1172/jci.insight.97500
Scopus Count
Collections
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International