PR1 peptide-HLA-A2 complex (PR1/HLA-A2)

The PR1 peptide-HLA-A2 complex is formed by the presentation of the PR1 peptide (a 9-mer derived from the myeloid cell proteins proteinase 3 and neutrophil elastase) in the peptide-binding groove of the human MHC class I molecule HLA-A2. This complex is presented on the surface of malignant myeloid cells, including those from patients with acute myeloid leukemia and chronic myeloid leukemia, as well as some myelodysplastic syndromes. The PR1/HLA-A2 complex serves as a target for cytotoxic T lymphocytes and TCR-like monoclonal antibodies such as 8F4, which recognize this complex specifically and can mediate lysis of leukemia cells without damaging most normal hematopoietic progenitors. The expression and immunogenicity of this complex have prompted the development of both peptide vaccines and antibody-based therapies targeting leukemia and possibly other HLA-A2+ cancers. Monitoring the presence of PR1/HLA-A2 on tumor cells and the frequency of PR1-specific T cells in patients can inform both patient selection and response to therapy.

Other names

PR1/HLA-A2PR1–HLA-A*0201 complexPR1 antigen-HLA-A2 complex

The PR1/HLA-A2 complex serves as a target for various therapeutic interventions. Binding of cytotoxic T cells leads to killing of malignant cells expressing the complex. Monoclonal antibodies, such as 8F4, bind specifically to the PR1/HLA-A2 complex, mediating both complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) against leukemia cells. Vaccine-mediated immune responses, such as with PR1 peptide vaccination, increase the PR1-specific CD8+ T-cell population, thereby enhancing immune recognition of leukemia cells.