Alloantigen-specific peptide–Major Histocompatibility Complex class I (pMHC-I)

Alloantigen-specific peptide–Major Histocompatibility Complex class I (pMHC-I) complexes are the fundamental molecular structures recognized by T cells during allogeneic immune responses, such as those occurring in organ transplantation or hematopoietic stem cell therapy (Janeway et al., 2001). These complexes consist of a polymorphic MHC class I molecule (Human Leukocyte Antigen or HLA in humans) and a short peptide derived from a protein that differs between the donor and the recipient (Shlomchik, 2007). In Graft-versus-Host Disease (GvHD), donor-derived T cells recognize these complexes on host antigen-presenting cells and tissues, leading to immune-mediated damage. Conversely, in transplant rejection, the recipient's immune system targets these complexes on donor-derived cells. Modern therapeutic approaches, including TCR-like antibodies and CAR-T cells, are being developed to target these specific pMHC-I complexes with high precision (He et al., 2021). By focusing on the unique peptide-MHC interface rather than the entire HLA molecule, these therapies aim to selectively deplete alloreactive T cells or protect the graft while minimizing broad immunosuppression and preserving general immunity (Shaffer et al., 2021). Monitoring these complexes and the T cells that bind them is critical for managing transplant outcomes and developing personalized immunotherapies (Pai et al., 2019).

Other names

Allo-pMHC complexPeptide-HLA class I complexAlloantigen-MHC complexMHC-peptide complexAllo-HLA-peptide complex

Selective binding to the peptide-MHC groove to either block T-cell recognition or induce targeted lysis of cells presenting the specific alloantigen.