Proteinase 3-derived peptide–Major Histocompatibility Complex class I (PR3-peptide-MHC-I)

The PR3-derived peptide–MHC class I complex is a specialized immunological target primarily relevant in myeloid malignancies such as acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Proteinase 3 (PR3), also known as myeloblastin, is a serine protease found in the primary granules of neutrophils and is significantly overexpressed in leukemic blasts. A specific 9-amino acid fragment of this protein, known as the PR1 peptide (VLQELNVTV), is processed and presented on the cell surface by the HLA-A*02:01 molecule. This peptide-MHC (pMHC) complex serves as a tumor-associated antigen that can be recognized by the cellular immune system. Therapeutic interventions targeting this complex include peptide-based vaccines intended to stimulate endogenous PR1-specific cytotoxic T lymphocytes and advanced biologics like TCR-like antibodies (e.g., h8F4) or chimeric antigen receptor (CAR) T cells. These therapies aim to exploit the differential expression of PR3 between leukemic cells and normal tissues, although the presence of PR3 in healthy mature neutrophils presents a potential risk for off-target effects and neutropenia.

Other names

PR1-HLA-A*02:01 complexPR1-MHC complexMyeloblastin-derived peptide-MHC complexPR3-pMHC

The complex acts as a ligand for T-cell receptors (TCRs) or TCR-like antibodies, triggering cytotoxic T-lymphocyte (CTL) mediated lysis or antibody-dependent cellular cytotoxicity (ADCC) against cells presenting the peptide.