Dickkopf-related protein 1 peptide-HLA-A*02:01 complex (DKK1-HLA-A2 complex)

The Dickkopf-related protein 1 (DKK1) peptide-HLA-A2 complex is a specific peptide-major histocompatibility complex (pMHC) presented on the surface of various malignant cells. DKK1 is a secreted glycoprotein that normally acts as a potent inhibitor of the Wnt/beta-catenin signaling pathway and is frequently overexpressed in cancers such as multiple myeloma, lung cancer, and breast cancer (1.1.2, 1.1.3). While DKK1 itself is a secreted protein, its intracellular processing leads to the presentation of specific immunogenic peptides, such as the P20 peptide (ALGGHPLLGV), by the HLA-A*02:01 molecule (1.2.2, 1.3.1). This complex serves as a highly specific tumor-associated antigen because its expression is largely restricted to tumor tissues, with minimal presence in normal adult tissues except for the placenta and testis (1.5.1). Therapeutic strategies targeting this complex include TCR-like monoclonal antibodies and chimeric antigen receptor (CAR) T-cells, which can bypass the limitations of targeting secreted proteins by recognizing the surface-bound pMHC (1.3.3, 1.4.1). These therapies induce potent anti-tumor responses through mechanisms like antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and direct apoptosis via the caspase-9 cascade (1.1.1, 1.3.1). Preclinical studies have highlighted the potential of this complex as a safe and effective target for precision immunotherapy in both hematological and solid tumors (1.4.2, 1.5.1).

Other names

DKK1-A2 complexDKK1-P20-HLA-A2 complexDKK1-MHC complexDKK1-HLA-A*0201DKK1-P20-HLA-A*02:01

Targeting of the DKK1 peptide-HLA-A2 complex on the cell surface to induce T-cell mediated cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), or direct apoptosis via the caspase-9 cascade.