PR1 peptide-Human Leukocyte Antigen-A*02:01 complex (PR1/HLA-A2)

The PR1/HLA-A2 complex is a prominent leukemia-associated antigen consisting of the PR1 nonamer peptide (VLQELNVTV) bound to the Human Leukocyte Antigen-A*02:01 molecule (Molldrem et al., 2000, Nature Medicine). The PR1 peptide is derived from two primary granule serine proteases, proteinase 3 and neutrophil elastase, which are overexpressed in myeloid leukemia blasts compared to normal hematopoietic progenitors (Sergeeva et al., 2011, Blood). This complex is presented on the surface of malignant cells, making it a highly specific target for immunotherapy in diseases such as acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Therapeutic strategies include PR1 peptide vaccines, which stimulate the patient's immune system to produce PR1-specific cytotoxic T lymphocytes, and TCR-like monoclonal antibodies like h8F4 that recognize the peptide-MHC complex with high affinity (Ma et al., 2016, JCI). Clinical studies have demonstrated that the presence of PR1-specific T cells correlates with molecular remission and the graft-versus-leukemia effect after stem cell transplantation. However, challenges remain regarding the low density of the complex on the cell surface and the potential for off-target effects on mature neutrophils (Alatrash et al., 2017, Journal for ImmunoTherapy of Cancer).

Other names

PR1-HLA-A2 complexVLQELNVTV-HLA-A*02:01PR1/A2PR1-MHC complex

Drugs targeting the PR1/HLA-A2 complex typically function by mimicking or enhancing T-cell receptor (TCR) recognition. This includes TCR-like antibodies (e.g., h8F4) that bind the complex to induce antibody-dependent cellular cytotoxicity (ADCC) or vaccines that expand endogenous PR1-specific cytotoxic T lymphocytes (CTLs) to selectively lyse leukemia cells (Sergeeva et al., 2011, Blood; Molldrem et al., 2003, Blood).