PR1 peptide–HLA-A*02:01 complex (PR1/HLA-A2)

The PR1 peptide–HLA-A*02:01 complex is a leukemia-associated antigen (LAA) consisting of a 9-amino acid peptide (VLQELNVTV) bound to the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule (Molldrem et al., 2000). The PR1 peptide is derived from proteinase 3 (P3) and neutrophil elastase (NE), which are primary granule proteins overexpressed in the blasts of patients with acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS) (Sergeeva et al., 2011). This complex is a critical target for immunotherapy because it is presented on the surface of malignant cells and can be recognized by the cellular immune system (Alatrash et al., 2012). Therapeutic approaches include PR1 peptide vaccines, which aim to expand endogenous PR1-specific cytotoxic T lymphocytes (CTLs), and adoptive cell therapies using T cells engineered with PR1-specific T-cell receptors (TCRs) (Ma et al., 2016). Additionally, TCR-like antibodies (e.g., h8F4) have been developed to bind the complex with high specificity, enabling antibody-mediated clearance of leukemia cells (Sergeeva et al., 2011). A significant clinical challenge is the potential for "on-target, off-tumor" toxicity, as the parent proteins are also found in normal mature neutrophils and their precursors, potentially leading to transient neutropenia (Molldrem et al., 2000).

Other names

PR1-HLA-A2 complexVLQELNVTV-HLA-A*02:01 complexProteinase 3/Neutrophil Elastase-derived peptide PR1-HLA-A*02:01PR1/A2

Induction of T-cell mediated cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) against leukemia cells presenting the PR1 peptide (Molldrem et al., 2000; Sergeeva et al., 2011).