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

The PR1 peptide-HLA-A*02:01 complex is a prominent leukemia-associated antigen consisting of the 9-amino acid peptide VLQELNVTV bound to the MHC class I molecule HLA-A*02:01 (Molldrem et al., 2000). This peptide is derived from the primary granule proteins Proteinase 3 (PRTN3) and Neutrophil Elastase (ELANE), which are aberrantly overexpressed in myeloid leukemia blasts compared to normal hematopoietic progenitors (Alatrash et al., 2012). While these parent proteins are also found in healthy mature neutrophils, the PR1 peptide is preferentially presented on the surface of malignant cells, creating a therapeutic window for immunotherapy. Therapeutic strategies targeting this complex include PR1 peptide vaccines, TCR-like monoclonal antibodies such as h8F4, and adoptive T-cell therapies (Sergeeva et al., 2011). Clinical studies have demonstrated that the induction of PR1-specific cytotoxic T lymphocytes correlates with molecular remission and the clearance of minimal residual disease in patients with Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML). However, a notable safety concern is the potential for transient neutropenia, as the target proteins are shared with healthy myeloid lineages. Overall, the PR1/HLA-A2 complex represents a critical target for developing precision immunotherapies in myeloid malignancies.

Other names

PR1-HLA-A*02:01VLQELNVTV peptide-MHC complexProteinase 3-derived PR1 peptideNeutrophil Elastase-derived PR1 peptide

The target is recognized by the T-cell receptor (TCR) of PR1-specific CD8+ T cells or by TCR-like antibodies (e.g., h8F4), leading to the targeted lysis of leukemia cells through the release of cytotoxic granules (perforin/granzyme) or induction of antibody-dependent cellular cytotoxicity (ADCC) (Molldrem et al., 2000; Sergeeva et al., 2011).