Allogeneic peptide–Major Histocompatibility Complex (allo-pMHC)

Allogeneic peptide–Major Histocompatibility Complex (pMHC) molecules are essential structures for the immune system's ability to distinguish between self and non-self. These complexes consist of a peptide fragment, derived from intracellular or extracellular proteins, presented on the cell surface by a Major Histocompatibility Complex (MHC) molecule, known as Human Leukocyte Antigen (HLA) in humans (Murphy & Weaver, Janeway's Immunobiology, 2016). In allogeneic hematopoietic stem cell transplantation, donor T cells recognize these allogeneic pMHCs on host cells, which can lead to the beneficial Graft-versus-Leukemia (GvL) effect or the detrimental Graft-versus-Host Disease (GvHD) (Ferrara et al., Lancet, 2009). Modern therapeutic interventions, such as TCR-engineered T cells (TCR-T) and TCR-like antibodies, are designed to target specific pMHCs that are uniquely or over-expressed on malignant cells (D'Angelo et al., Lancet, 2024). By focusing on these specific complexes, researchers aim to direct the immune response toward tumors while sparing healthy tissues (Nathan et al., N Engl J Med, 2021). This target is central to the development of precision immunotherapies for both solid tumors and hematologic malignancies.

Other names

Allo-pMHCAllogeneic HLA-peptide complexMinor histocompatibility antigen complexMHC-peptide complex

Targeted immune-mediated cytotoxicity via T-cell receptor (TCR) or TCR-mimetic binding to the peptide-MHC complex, facilitating T-cell activation and lysis of the target cell.