Allorecognition Unveiled: Integrating Recent Breakthroughs Into the Current Paradigm

In transplantation, genetic differences between donor and recipient trigger immune responses that cause graft rejection. Allorecognition, the process by which the immune system discriminates allogeneic grafts, targets major histocompatibility complex (MHC) and minor histocompatibility antigens. Hist...

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Bibliographic Details
Published in:Transplant international 2024-11, Vol.37, p.13523
Main Authors: Charmetant, Xavier, Pettigrew, Gavin J, Thaunat, Olivier
Format: Article
Language:English
Subjects:
adaptive immunity
Adaptive Immunity - immunology
allorecognition pathways
Animals
Antigen-Presenting Cells - immunology
B-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - immunology
graft rejection
Graft Rejection - immunology
Health Archive
Humans
Immunity, Innate
innate immunity
Isoantigens - immunology
Killer Cells, Natural - immunology
Major Histocompatibility Complex - immunology
Myeloid Cells - immunology
Organ Transplantation
pathophysiology
Transplantation Immunology
Transplantation, Homologous
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Summary:In transplantation, genetic differences between donor and recipient trigger immune responses that cause graft rejection. Allorecognition, the process by which the immune system discriminates allogeneic grafts, targets major histocompatibility complex (MHC) and minor histocompatibility antigens. Historically, it was believed that allorecognition was solely mediated by the recipient's adaptive immune system recognizing donor-specific alloantigens. However, recent research has shown significant roles for innate immune components, such as lymphoid and myeloid cells, which are sometimes triggered by the mere absence of a self-protein in the graft. This review integrates recent breakthroughs into the current allorecognition paradigm based on the well-established direct and indirect pathways, emphasizing the semi-direct pathway where recipient antigen-presenting cells (APCs) acquire donor MHC molecules, and the inverted direct pathway where donor CD4 T cells within the graft activate recipient B cells to produce donor-specific antibodies (DSAs). The review also explores the role of natural killer (NK) cells in both promoting and inhibiting graft rejection, highlighting their dual role in innate allorecognition. Additionally, it discusses the emerging understanding of myeloid cell-mediated allorecognition and its implications for initiating adaptive immune responses. These insights aim to provide a more comprehensive understanding of allorecognition, potentially leading to improved transplant outcomes.
ISSN:1432-2277
0934-0874
1432-2277
DOI:10.3389/ti.2024.13523