Proteinase 3-derived PR1 epitope presented by HLA-A*02:01 (PR1/HLA-A*02:01)

The PR1/HLA-A*02:01 complex is a well-characterized leukemia-associated antigen (LAA) that serves as a critical target for T-cell based immunotherapies. It consists of the nonameric peptide PR1 (sequence: VLQELNVTV), which is derived from the azurophilic granule proteins proteinase 3 (PR3) and myeloperoxidase (MPO), presented on the cell surface by the human leukocyte antigen (HLA)-A*02:01 molecule (Molldrem et al., 1996, Blood). While PR3 and MPO are endogenously expressed in normal myeloid cells, they are significantly overexpressed in the blasts of patients with acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS), leading to a higher density of the PR1/HLA-A*02:01 complex on malignant cells (Rezvani et al., 2008, Blood). Therapeutic targeting of this complex has been explored through various modalities, including PR1 peptide vaccines, which have shown the ability to elicit PR1-specific cytotoxic T-lymphocyte (CTL) responses that correlate with clinical remission (Molldrem et al., 2000, Nature Medicine). Additionally, advanced strategies such as TCR-engineered T cells and TCR-like antibodies (e.g., 8F4) are being developed to bypass the need for endogenous immune activation and directly target the pMHC complex on leukemic cells (Sergeeva et al., 2016, Frontiers in Immunology). The specificity of this target for myeloid malignancies makes it a high-priority candidate for treating HLA-A*02:01 positive patients with refractory or relapsed leukemia.

Other names

PR1-HLA-A2 complexPR1 peptide-MHC complexVLQELNVTV-HLA-A*02:01PR1/A2Proteinase 3 (169-177) presented by HLA-A*02:01

The target acts as a specific molecular flag on the surface of malignant myeloid cells, allowing for recognition and lysis by PR1-specific cytotoxic T lymphocytes (CTLs) or TCR-like therapeutic agents. Drugs targeting this complex aim to induce or provide a T-cell mediated immune response specifically against leukemia cells overexpressing the parent proteins proteinase 3 and myeloperoxidase.