HLA-A*02:01-presented PR1 peptide complex (PR1/HLA-A*02:01)

The HLA-A*02:01-presented PR1 peptide complex is a leukemia-associated antigen consisting of the 9-amino acid peptide PR1 (VLQELNVTV) bound to the HLA-A*02:01 MHC class I molecule (Molldrem et al., Nature Medicine, 2000). The PR1 peptide is derived from the azurophilic granule proteases proteinase 3 (PR3) and neutrophil elastase (NE), which are overexpressed in myeloid leukemias such as acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) (Molldrem et al., Blood, 1996). This complex is a target for the immune system, naturally recognized by cytotoxic T lymphocytes (CTLs) that contribute to the graft-versus-leukemia (GVL) effect after stem cell transplantation. Therapeutic approaches targeting this complex include PR1 peptide vaccines, TCR-like antibodies such as h8F4, and adoptive T-cell therapies using PR1-specific T-cell receptors (Sergeeva et al., Blood, 2011). Because the target is a peptide-MHC complex, it enables the targeting of intracellular proteins that are otherwise inaccessible to standard monoclonal antibodies. Clinical use is restricted to patients who are HLA-A*02:01 positive and requires monitoring for potential off-target effects on healthy myeloid cells that also express the parent proteins.

Other names

PR1/HLA-A2 complexPR1-MHC complexProteinase 3-derived PR1 peptide-HLA-A*02:01 complexVLQELNVTV-HLA-A*02:01PR1-HLA-A2

Induction of T-cell mediated lysis of leukemia cells and antibody-dependent cellular cytotoxicity (ADCC) targeting cells presenting the PR1 peptide.