How T cells recognize alloantigen: evidence for two pathways of allorecognition.
During allograft rejection, both allorecognition pathways seem to be effective. The direct pathway, where T-cell receptors directly recognize intact allo-MHC with or without bound peptides on the surface of target cells, accounts for most of the cytotoxic T cell function. The indirect pathway in contrast, where T-cell receptors recognize MHC allopeptides after processing and presentation by self APCs, may lead to the activation of T helper cells which secrete cytokines and provide the necessary signals for the growth and maturation of effector cytotoxic T lymphocytes and B cells leading to allograft rejection. The role of the indirect pathway is supported by the findings that mouse skin transplants from a class II deficient donor can be rejected involving CD4+ self-restricted T-cell recognition of donor antigen. In addition, rats primed by class I MHC peptides do reject skin grafts as well as renal allografts in an accelerated fashion. Studies showing that synthetic class II peptides can also be used to tolerize animals for a subsequent renal transplant further underline the importance of this self restricted recognition of allo-MHC. More studies are needed to better define the contribution of this self-restricted T cell recognition of processed allo-MHC to the rejection process in particular in regard to its suggested role in chronic allograft failure as well as to its susceptibility to therapeutic regimens in organ transplant recipients.
Watschinger
B
B
Department of Medicine, University of Vienna, Austria.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D006801:Humans; D007519:Isoantigens; D051379:Mice; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens