Human leukocyte antigen A*02:01-PR1 peptide complex (HLA-A2-PR1)

The HLA-A2-PR1 complex is a specific peptide-major histocompatibility complex (pMHC) consisting of the HLA-A*02:01 molecule and the PR1 peptide (VLQELNVTV) (Molldrem et al., 2000, Nature Medicine). The PR1 peptide is a 9-amino acid epitope derived from the azurophilic granule proteins proteinase 3 and neutrophil elastase, which are significantly overexpressed in myeloid leukemia cells compared to normal hematopoietic cells (Sergeeva et al., 2011, Blood). This differential expression allows the HLA-A2-PR1 complex to serve as a leukemia-associated antigen (LAA) for targeted immunotherapy. Therapeutic approaches include the PR1 peptide vaccine, which stimulates endogenous T-cell responses, and TCR-like monoclonal antibodies such as 8F4 that recognize the pMHC complex directly (Ma et al., 2016, Cancer Cell). These agents work by recognizing the specific conformation of the peptide within the MHC groove to trigger antibody-dependent cellular cytotoxicity (ADCC) or T-cell mediated lysis. Clinical applications primarily focus on treating acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). A primary safety concern is the potential for off-target effects on healthy myeloid progenitor cells, which also express the source proteins, potentially leading to transient neutropenia.

Other names

PR1/HLA-A2 complexHLA-A*02:01-PR1PR1-MHC complexProteinase 3/Neutrophil Elastase-derived peptide PR1 in complex with HLA-A2

TCR-like antibodies or T-cell receptors bind specifically to the PR1 peptide presented within the HLA-A*02:01 molecule, triggering antibody-dependent cellular cytotoxicity (ADCC) or direct T-cell mediated lysis of the target cell (Sergeeva et al., 2011, Blood).