Donor Human Leukocyte Antigen (HLA) and Recipient T-cell Receptor (TCR) Complex (HLA-TCR Complex)

The interaction between donor Human Leukocyte Antigen (HLA) molecules and recipient T-cell receptors (TCR) is the fundamental immunological event in solid organ transplantation and hematopoietic stem cell transfer (Source: Murphy K, Weaver C. Janeway's Immunobiology. 9th ed. Garland Science; 2016). HLA molecules, also known as Major Histocompatibility Complex (MHC) proteins, are expressed on the surface of donor cells and present peptides to the recipient's T-cells (Source: NIH, National Institute of Allergy and Infectious Diseases). When the recipient's TCR recognizes the donor HLA-peptide complex as non-self—a process known as allorecognition—it triggers a robust immune response (Source: Ingulli E. Mechanism of cellular rejection in transplantation. Pediatr Nephrol. 2010;25(1):61-74). This response leads to T-cell proliferation, cytokine production, and the eventual destruction of the transplanted tissue, manifesting as graft rejection (Source: Nankivell BJ, Alexander SI. Rejection of the kidney allograft. N Engl J Med. 2010;363(15):1451-62). Conversely, in bone marrow transplants, donor T-cells may recognize recipient HLA, resulting in graft-versus-host disease (Source: Zeiser R, Blazar BR. Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy. N Engl J Med. 2017;377(22):2167-2179). Therapeutic strategies targeting this interaction include broad immunosuppressants that inhibit downstream TCR signaling, such as calcineurin inhibitors, and more specific biologics like belatacept that block necessary costimulatory signals (Source: Vincenti F, et al. Belatacept and Long-Term Outcomes in Kidney Transplantation. N Engl J Med. 2016;374:333-343).

Other names

HLA-TCR interactionMHC-TCR complexAlloantigen-TCR complexDonor-recipient immune synapse

Inhibition of calcineurin-mediated T-cell activation, blockade of CD80/CD86-CD28 costimulation, depletion of T-lymphocytes, and inhibition of IL-2 receptor signaling.