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Continuous Acquisition of MHC :Peptide Complexes by Recipient Cells Contributes to the Generation of Anti‐Graft CD 8 + T Cell Immunity
Author(s) -
Smyth L. A.,
Lechler R. I.,
Lombardi G.
Publication year - 2017
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13996
Subject(s) - allorecognition , major histocompatibility complex , cytotoxic t cell , cd8 , immunology , transplantation , mhc class i , t cell , medicine , immune system , antigen , biology , microbiology and biotechnology , genetics , in vitro
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 ( DC s), 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 DC s during the life span of a skin graft. We observed that MHC‐class I acquisition by recipient DC s occurs for at least 1 month following transplantation and may be the main source of alloantigen that drives CD 8 + 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.