Dickkopf-related protein 1-derived peptides presented on MHC molecules (DKK1-pMHC)

Dickkopf-related protein 1 (DKK1) is a secreted protein that acts as a potent antagonist of the canonical Wnt/beta-catenin signaling pathway by binding to the LRP5/6 receptors (UniProt P57073). While DKK1 plays a critical role in embryonic development and bone formation, it is frequently overexpressed in various malignancies, including multiple myeloma and prostate cancer, where it contributes to tumor progression and osteolytic bone lesions (PubMed: 14695414). Peptides derived from the intracellular processing of DKK1 are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, particularly the HLA-A*02:01 allele. These DKK1-pMHC complexes serve as highly specific tumor-associated antigens that can be recognized by the T-cell receptor (TCR) of cytotoxic T lymphocytes (PubMed: 22130638). Therapeutic strategies targeting these complexes include peptide-based vaccines and TCR-engineered T cells, which aim to trigger a robust immune response specifically against DKK1-expressing cancer cells while minimizing damage to normal tissues (PubMed: 35115524). This target is particularly valuable in immunotherapy because DKK1 expression is often restricted in healthy adult tissues but highly prevalent in the 'stem-like' cells of many aggressive cancers.

Other names

DKK1 peptide-HLA complexDKK1-derived MHC-restricted peptidesDKK1-HLA-A*02:01 complexDickkopf-1 antigenDKK1-pHLA

Induction of antigen-specific cytotoxic T lymphocyte (CTL) responses against cells presenting DKK1-derived peptides on MHC molecules, leading to targeted cell lysis and tumor reduction.