Proteinase 3 peptide–MHC class I complex (PR3–MHC I complex)

The Proteinase 3 (PR3) peptide–MHC class I complex is a specialized immunological target consisting of a peptide fragment derived from the PR3 protein—most commonly the PR1 peptide (VLQELNVTV)—bound to a Major Histocompatibility Complex (MHC) class I molecule, typically HLA-A*02:01 (Molldrem et al., Nature Medicine, 2000). PR3 is a serine protease normally sequestered in neutrophil granules but is significantly overexpressed in the cytoplasm and on the surface of myeloid leukemia cells, including those in Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML) (Rezvani et al., Blood, 2008). This complex serves as a neoantigen-like target that can be recognized by the cellular immune system, specifically by cytotoxic T lymphocytes (CTLs). Therapeutic interventions targeting this complex include PR1 peptide vaccines, T-cell receptor (TCR)-like monoclonal antibodies such as 8F4, and TCR-engineered T-cell therapies (Ma et al., Cancer Cell, 2016). These treatments aim to induce targeted lysis of leukemic cells while sparing non-myeloid tissues. However, because PR3 is also expressed at lower levels in healthy bone marrow precursors, clinical development must carefully monitor for potential hematopoietic toxicity and neutropenia (Sergeeva et al., Blood, 2011).

Other names

PR1–HLA-A*02:01 complexPR1–HLA-A2 complexMyeloblastin peptide–MHC complexPR3–HLA-A2 complexProteinase 3–HLA-A*02:01 complex

Induction of cytotoxic T-lymphocyte (CTL) mediated lysis or antibody-dependent cellular cytotoxicity (ADCC) by specifically recognizing the PR3-derived peptide (PR1) presented on the cell surface by MHC class I molecules.