PR1 peptide-HLA-A*0201 complex (PR1/HLA-A2)

The PR1 peptide-HLA-A*0201 complex is a prominent leukemia-associated antigen (LAA) target for immunotherapy in myeloid malignancies (Molldrem et al., Nature Medicine, 2000). PR1 is a 9-amino acid peptide (VLQELNVTV) derived from the azurophilic granule proteins proteinase 3 (PR3) and neutrophil elastase (NE), which are aberrantly overexpressed in myeloid leukemia cells such as those in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) (Alatrash et al., Expert Rev Hematol, 2012). These proteins are processed and presented on the cell surface by the HLA-A*0201 molecule, providing a specific target for the immune system. Because the PR1/HLA-A2 complex is presented at higher densities on leukemic blasts than on normal hematopoietic progenitors, it creates a therapeutic window for T-cell-based interventions (Rezvani et al., Blood, 2008). Therapeutic strategies targeting this complex include PR1 peptide vaccines, adoptive transfer of PR1-specific cytotoxic T lymphocytes (CTLs), and TCR-like antibodies such as 8F4 that mimic T-cell receptor specificity (Sergeeva et al., Blood, 2011). While these therapies aim to selectively eliminate malignant cells, potential safety concerns include transient neutropenia due to the expression of the parent proteins in mature neutrophils (Molldrem et al., Blood, 1997).

Other names

PR1 peptideVLQELNVTV peptideProteinase 3-derived peptide PR1Neutrophil elastase-derived peptide PR1PR1-HLA complexPR1-HLA-A2

Induction of T-cell mediated cytotoxicity or antibody-dependent cellular cytotoxicity (ADCC) against cells presenting the PR1 peptide in the context of HLA-A*0201 (Sergeeva et al., Blood, 2011).