Dickkopf-1 P20 peptide–HLA-A*02:01 complex (DKK1-P20/HLA-A*02:01)

The DKK1 P20 peptide–HLA-A*02:01 surface complex is a tumor-associated antigen consisting of a specific 9-amino acid epitope (ALMESFEVV) derived from the Dickkopf-1 (DKK1) protein, presented by the HLA-A*02:01 major histocompatibility complex (PMID: 22964305). DKK1 is a secreted glycoprotein and a potent inhibitor of the Wnt/beta-catenin signaling pathway, frequently overexpressed in multiple myeloma and various solid tumors where it promotes tumor growth and osteolytic bone destruction (PMID: 21540470). Because DKK1 is an intracellularly synthesized protein, its presentation as a peptide-MHC complex allows the immune system to recognize and target malignant cells from the outside. Therapeutic strategies targeting this complex include TCR-like monoclonal antibodies and chimeric antigen receptor (CAR) T cells, which are engineered to bind the pMHC complex with high specificity, mimicking the natural recognition mechanism of T-cell receptors (PMID: 22964305). This target is highly specific to patients carrying the HLA-A*02:01 allele, and its differential expression between cancerous and healthy adult tissues makes it a promising candidate for precision immunotherapy.

Other names

DKK1-P20/A2ALMESFEVV-HLA-A*02:01 complexDKK1 peptide-MHC complexDKK1-P20-HLA-A2

TCR-like recognition of the peptide-MHC complex on the cell surface, leading to targeted cell lysis via antibody-dependent cellular cytotoxicity (ADCC) or direct T-cell mediated cytotoxicity.