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

The PR1 peptide presented by HLA-A2 is a prominent leukemia-associated antigen complex that serves as a target for immunotherapy in myeloid malignancies. PR1 is a 9-amino acid peptide (VLQELNVTV) derived from the azurophilic granule proteins proteinase 3 and neutrophil elastase, which are overexpressed in the blasts of patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) (Molldrem et al., 2000, Nature Medicine). This peptide is presented on the cell surface by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule, allowing it to be recognized by specific CD8+ cytotoxic T lymphocytes (Sergeeva et al., 2011, Blood). Therapeutic strategies targeting this complex include PR1 peptide vaccines, TCR-like monoclonal antibodies such as h8F4, and engineered T-cell therapies (Ma et al., 2016, Cancer Research). Clinical evidence suggests that the presence of PR1-specific T cells correlates with the induction of remission and the maintenance of minimal residual disease negativity in leukemia patients. However, because the source proteins are also expressed in healthy mature neutrophils, a significant safety concern is the potential for treatment-induced neutropenia or damage to normal myeloid progenitors.

Other names

PR1-HLA-A2 complexVLQELNVTV-HLA-A*02:01PR1/A2 complexProteinase 3-derived PR1 peptide-MHC complex

Induction of antigen-specific cytotoxic T-lymphocyte response or direct targeting via TCR-like antibodies to induce cell lysis.