Continuous acquisition of MHC:peptide complexes by recipient cells contributes to the generation of anti-graft CD8+T cell immunity

Article


Smyth, L., Lechler, Robert I and Lombardi, Giovanna 2016. Continuous acquisition of MHC:peptide complexes by recipient cells contributes to the generation of anti-graft CD8+T cell immunity. American Journal of Transplantation. 17 (1), pp. 60-68.
AuthorsSmyth, L., Lechler, Robert I and Lombardi, Giovanna
Abstract

Understanding the evolution of the direct and indirect pathways of allorecognition following tissue transplantation is essential in the design of tolerance-promoting protocols. On the basis that donor bone marrow-derived antigen presenting cells are eliminated within days of transplantation, it has been argued that the indirect response represents the major threat to long term transplant survival, and is consequently the key target for regulation. However, the detection of MHC transfer between cells, and particularly the capture of MHC:peptide complexes by dendritic cells, led us to propose a third, semi-direct, pathway of MHC allorecognition. Persistence of this pathway would lead to sustained activation of direct pathway T cells, arguably persisting for the life of the transplant. In this study, we focused on the contribution of acquired MHC class I, on recipient DCs, during the life span of a skin graft. We observed that MHC class I acquisition by recipient DCs occurs for at least one month following transplantation and may be the main source of alloantigen that drives CD8+ cytotoxic T cell responses. In addition, acquired MHC class I-peptide complexes stimulate T cell responses in vivo further emphasizing the need to regulate both pathways to induce indefinite survival of the graft.

JournalAmerican Journal of Transplantation
Journal citation17 (1), pp. 60-68
ISSN16006135
Year2016
PublisherWiley
Accepted author manuscript
File Access Level
Repository staff only
Publisher's version
License
Digital Object Identifier (DOI)doi:10.1111/ajt.13996
Publication dates
Print06 Aug 2016
Online28 Dec 2016
Publication process dates
Deposited10 Aug 2016
Accepted26 Jul 2016
Accepted26 Jul 2016
FunderBritish Heart Foundation
National Institute for Health Research
British Heart Foundation
National Institute for Health Research
Copyright information© 2016 The authors
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