Donor-derived alloantigenic peptide–Major Histocompatibility Complex (Donor pMHC)

Donor-derived alloantigenic peptide–Major Histocompatibility Complex (pMHC) molecules are the fundamental units recognized by the recipient's immune system during allograft rejection (Gould and Auchincloss, 1999). These complexes comprise a donor-derived MHC molecule (Human Leukocyte Antigen or HLA in humans) bound to a specific peptide fragment (Janeway et al., 2001). Recognition occurs via the direct pathway, where recipient T cells interact with intact donor pMHC on the surface of donor cells, or the indirect pathway, where donor MHC proteins are processed and presented by recipient antigen-presenting cells (Afzali et al., 2007). This interaction triggers a robust T-cell mediated immune response, leading to graft destruction or graft-versus-host disease (GVHD) (Wood and Sakaguchi, 2003). Therapeutic interventions traditionally involve broad immunosuppressants like calcineurin inhibitors (e.g., tacrolimus) or costimulation blockers (e.g., belatacept) to mitigate this response (Vincenti et al., 2011). Emerging precision therapies, including TCR-like antibodies and regulatory T-cell (Treg) therapies, aim to specifically target or modulate the recognition of these alloantigenic complexes to improve transplant longevity and reduce systemic toxicity (Nolan et al., 2020).

Other names

Donor HLA-peptide complexAllo-pMHCDonor-derived MHC-peptide complexAllogeneic pMHCDonor-derived alloantigenic pMHC

Inhibition of the interaction between the T-cell receptor (TCR) and the donor pMHC complex, or suppression of downstream signaling pathways and costimulatory signals required for T-cell activation (Vincenti et al., 2011; Halloran, 2004).