Neutrophil elastase-derived PR1 peptide-HLA-A*0201 complex (PR1)

The Neutrophil elastase-derived PR1 epitope is a 9-amino acid peptide (VLQELNVTV) derived from the azurophilic granule proteins neutrophil elastase (NE) and proteinase 3 (PR3) (Molldrem et al., 2000, Nature Medicine). This epitope is presented on the cell surface by the human leukocyte antigen HLA-A*0201 and serves as a prominent leukemia-associated antigen (LAA) (Rezvani et al., 2008, Blood). It is highly expressed on the surface of myeloid leukemia cells, including those in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), due to the overexpression and aberrant processing of NE and PR3 in these malignant cells (Molldrem et al., 1996, Blood). Because PR1-specific cytotoxic T lymphocytes (CTLs) can selectively kill leukemic cells while sparing normal hematopoietic stem cells, it has become a significant target for immunotherapy (Molldrem et al., 2000, Nature Medicine). Therapeutic strategies include PR1 peptide vaccines, TCR-like monoclonal antibodies such as h8F4, and adoptive T-cell therapies (Sergeeva et al., 2011, Blood; Ma et al., 2016, Cancer Research). Clinical trials have demonstrated that the elicitation of PR1-specific immune responses correlates with clinical remission in leukemia patients (Rezvani et al., 2008, Blood). However, potential safety concerns include transient neutropenia, as the source proteins are also present in healthy mature neutrophils and myeloid precursors (Sergeeva et al., 2011, Blood).

Other names

PR1 peptideVLQELNVTVHLA-A*0201-restricted PR1 epitopePR1-HLA-A2 complex

Induction of cytotoxic T-lymphocyte (CTL) mediated lysis of cells presenting the PR1 peptide via HLA-A*0201.