Neutrophil elastase-derived peptide-HLA-A*02:01 complex (PR1-HLA-A2)

Neutrophil elastase-derived peptide antigens presented on MHC molecules are a class of leukemia-associated antigens used as targets for immunotherapy. The most prominent example is the PR1 peptide, a 9-amino acid sequence derived from both neutrophil elastase (ELANE) and proteinase 3 (PRTN3) (Molldrem et al., 2000, Nature Medicine). These antigens are overexpressed in myeloid leukemias, such as acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), where they are presented on the cell surface by HLA-A*02:01 (Ma et al., 2016, Cancer Cell). Because these proteins are essential components of neutrophil granules, their processed peptides serve as specific markers for myeloid lineage cells. Therapeutic strategies include TCR-like monoclonal antibodies, such as h8F4, which bind the peptide-MHC complex with high specificity to trigger immune-mediated cell death (Rezvani et al., 2008, Blood). Other approaches involve peptide vaccines and adoptive T-cell therapies designed to enhance the host's T-cell response against leukemic blasts. A significant challenge in targeting these antigens is the potential for off-target effects on healthy mature neutrophils and hematopoietic progenitor cells, which can lead to transient neutropenia (Sergeeva et al., 2011, Clinical Cancer Research). Despite this, the higher density of presentation on malignant cells compared to healthy cells provides a viable therapeutic window for clinical application.

Other names

PR1-MHC complexHLA-A*02:01-restricted PR1 peptideELANE-derived peptide antigenNeutrophil elastase-derived peptide-MHC class I complexPR1-HLA complex

Targeting of the specific peptide-MHC complex by T-cell receptors (TCRs) or TCR-like monoclonal antibodies to induce selective lysis of leukemic cells via T-cell mediated cytotoxicity or antibody-dependent cellular cytotoxicity (ADCC).