Proteinase 3 peptide (VLQELNVTV) presented by HLA-A*02:01 (PR1/HLA-A*02:01)

The Proteinase 3 epitope VLQELNVTV, widely referred to as the PR1 peptide, is a human leukocyte antigen (HLA)-A*02:01-restricted epitope derived from the primary granule protein Proteinase 3 (PR3) (Molldrem et al., Nature Medicine, 2000). PR3 is a serine protease that is highly overexpressed in the malignant blasts of myeloid leukemias, including acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), compared to normal hematopoietic cells (UniProt P24158). The PR1/HLA-A*02:01 complex acts as a tumor-associated antigen, making it a primary target for various immunotherapeutic approaches such as peptide-based vaccines and T-cell receptor (TCR) gene therapies (Rezvani et al., Blood, 2007). Research has shown that PR1-specific cytotoxic T lymphocytes (CTLs) can effectively lyse leukemia cells while showing relatively low toxicity toward normal bone marrow progenitors (Alatrash et al., Current Hematologic Malignancy Reports, 2012). Monoclonal antibodies, specifically TCR-like antibodies such as h8F4, have also been developed to target this specific peptide-MHC complex directly (Sergeeva et al., Blood, 2011). Despite its promise, therapeutic targeting faces challenges such as potential on-target off-tumor effects on healthy neutrophils and the development of immune resistance through HLA loss (Alatrash et al., 2012). This target represents a significant opportunity for precision immunotherapy in HLA-A*02:01 positive leukemia patients.

Other names

PR1 peptidePR1/HLA-A2 complexProteinase 3 (169-177) epitopeVLQELNVTV-HLA-A*02:01Myeloblastin epitope VLQELNVTV

Targeted lysis of cells presenting the PR1/HLA-A*02:01 complex through T-cell receptor recognition or TCR-like antibody binding, triggering apoptosis in malignant myeloid cells.