Human leukocyte antigen A*02:01 presenting PR1 peptide (VLQELNVTV) (HLA-A*02:01/PR1)

The HLA-A*02:01 presenting PR1 peptide epitope is a prominent leukemia-associated antigen complex used in targeted immunotherapy. The PR1 peptide is a 9-amino acid sequence (VLQELNVTV) derived from the azurophilic granule proteins proteinase 3 (PR3) and neutrophil elastase (NE), which are overexpressed in myeloid leukemias such as acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) [1][2]. This peptide is presented on the cell surface by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule, making it a specific target for cytotoxic T lymphocytes (CTLs) [1]. Therapeutic strategies targeting this complex include peptide vaccines, TCR-like monoclonal antibodies such as 8F4, and engineered TCR-T cell therapies [2][3]. Because PR3 and NE are also present in normal mature neutrophils, a key challenge is managing potential off-tumor effects while maximizing the destruction of leukemic blasts [3]. This target is highly specific to HLA-A*02:01-positive patients, necessitating companion diagnostic testing for patient selection [2]. Citations: [1] Molldrem JJ, et al. Nature Medicine. 2000;6(9):1018-1023. [2] Sergeeva A, et al. Blood. 2016;127(21):2595-2605. [3] Ma Q, et al. Journal of Hematology & Oncology. 2016;9:121.

Other names

PR1/HLA-A2 complexPR1-MHCProteinase 3-derived peptide PR1 in complex with HLA-A*02:01VLQELNVTV/HLA-A*02:01PR1-HLA-A*0201

Recognition of the specific peptide-MHC complex by T-cell receptors (TCRs) or TCR-like antibodies to induce targeted lysis of malignant myeloid cells.