Proteinase 3 peptide–HLA-A2 complex

The Proteinase 3 peptide–HLA-A2 complex is a molecular complex consisting of a peptide derived from Proteinase 3 (PR3)—a serine protease expressed in myeloid cells—bound to the human leukocyte antigen A*02 (HLA-A2), a class I major histocompatibility complex (MHC) molecule. This complex presents the PR3-derived peptide at the cell surface for recognition by CD8+ T cells. Antigenic peptides from Proteinase 3, such as the PR1 peptide, are frequently presented by HLA-A2 on myeloid leukemia cells and are targets for immunotherapy approaches including T cell–engaging bispecific antibodies (such as CG1/A2xCD3), vaccines, and TCR mimic antibodies[4][9]. The interaction between TCRs and these peptide–HLA-A2 complexes mediates antigen-specific immunity, contributing to anti-tumor responses or, potentially, immunopathology if presented by non-malignant cells[4][9]. Note: This target is highly specific and relevant as an immunotherapeutic epitope in HLA-A2-positive patients with myeloid neoplasms but is only relevant for patients presenting both Proteinase 3 expression and HLA-A2 genotype[4][9].

Other names

PR3 peptide–HLA-A2 complexPR1/HLA-A2 complex (where PR1 is a specific peptide derived from Proteinase 3)pMHC (peptide–major histocompatibility complex, when context is clear)

Targeted immunotherapy (bispecific antibody engages this pMHC complex and redirects T cells to kill presenting cells)[4] T cell receptor (TCR)-mediated recognition leading to cytotoxic CD8+ T cell responses