Direct recognition of hepatocyte-expressed MHC class I alloantigens is required for tolerance induction.
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.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Bunker, Daniel L J
Tay, Szun Szun
Logan, Grant J
Alexander, Ian E
Alexander, Stephen I
Sparwasser, Tim D
Bowen, David G
Bishop, G Alex
MetadataShow full item record
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.
CitationJCI Insight. 2018 Aug 9;3(15). pii: 97500. doi: 10.1172/jci.insight.97500. eCollection 2018 Aug 9.
AffiliationTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Alloantigen gene transfer to hepatocytes promotes tolerance to pancreatic islet graft by inducing CD8<sup>+</sup> regulatory T cells.
- Authors: Le Guen V, Judor JP, Boeffard F, Gauttier V, Ferry N, Soulillou JP, Brouard S, Conchon S
- Issue date: 2017 Apr
- Role of CD4+ and CD8+ T cells in allorecognition: lessons from corneal transplantation.
- Authors: Boisgérault F, Liu Y, Anosova N, Ehrlich E, Dana MR, Benichou G
- Issue date: 2001 Aug 15
- Indirect T cell recognition in allograft rejection.
- Authors: Bradley JA
- Issue date: 1996
- Prevention of allogeneic marrow graft rejection by donor T cells that do not recognize recipient alloantigens: potential role of a veto mechanism.
- Authors: Martin PJ
- Issue date: 1996 Aug 1
- Peptides derived from alpha-helices of allogeneic class I major histocompatibility complex antigens are potent inducers of CD4+ and CD8+ T cell and B cell responses after cardiac allograft rejection.
- Authors: Shirwan H, Leamer M, Wang HK, Makowka L, Cramer DV
- Issue date: 1995 Feb 15