title: Continuous Acquisition of MHC:Peptide Complexes by Recipient Cells Contributes to the Generation of Anti-Graft CD8+T Cell Immunity.
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 (DCs), led us to propose a third, semidirect, 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 1 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.
authors: Medical Research Council (MRC) Centre for Transplantation, King's College London, London, UK.|National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust and King's College London, London, UK.|School of Health, Sport and Bioscience, University of East London, London, UK.
authors: L A
authors: LA
authors: Smyth
authors: Medical Research Council (MRC) Centre for Transplantation, King's College London, London, UK.|National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust and King's College London, London, UK.
authors: R I
authors: RI
authors: Lechler
authors: Medical Research Council (MRC) Centre for Transplantation, King's College London, London, UK.|National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust and King's College London, London, UK.
authors: G
authors: G
authors: Lombardi
mesh_terms: D064591:Allografts; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology*; D016038:Skin Transplantation / Q000009:adverse effects*; D014019:Tissue Donors; D066027:Transplant Recipients
chemical_list: D007519:Isoantigens; D010446:Peptide Fragments
keywords: basic (laboratory) research/science; cytotoxicity; histocompatibility; immune regulation; immunobiology; immunosuppression/immune modulation; innate immunity