Proteinase 3-derived peptide-HLA-A*02:01 complex (PR1/HLA-A2)

Proteinase 3 (PR3) is a serine protease primarily found in neutrophil azurophilic granules (UniProt P24158). A specific 9-amino acid peptide derived from PR3, known as PR1 (VLQELNVTV), is presented on the cell surface by MHC class I molecules, specifically HLA-A*02:01 (Molldrem et al., Nature Medicine, 2000). This PR1/HLA-A2 complex is highly expressed on the surface of myeloid leukemia cells, including those in Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML), making it a significant leukemia-associated antigen (Rezvani et al., Blood, 2008). Therapeutic approaches targeting this complex include the PR1 peptide vaccine, which aims to elicit a host cytotoxic T-lymphocyte (CTL) response, and TCR-like monoclonal antibodies such as h8F4 that bind the peptide-MHC complex directly (Sergeeva et al., Blood, 2011). While effective in targeting leukemic blasts, the expression of PR3 in normal mature neutrophils presents a potential risk for off-target neutropenia, although clinical studies have suggested a therapeutic window exists due to higher expression levels on malignant cells (Molldrem et al., 2000). Additionally, PR3 is a well-known autoantigen in Granulomatosis with polyangiitis, which necessitates careful monitoring for autoimmune side effects during therapy (Kallenberg, Nature Reviews Rheumatology, 2014).

Other names

PR1-HLA-A2 complexMyeloblastin-derived peptide-MHC complexPR3-peptide-MHC class IPR1/HLA-A*02:01

Induction of cytotoxic T-lymphocyte response or direct antibody-mediated targeting of cells presenting the PR3-derived peptide on MHC class I molecules.