Major histocompatibility complex peptide-binding grooves bound by Mucin 4-derived peptides (MHC-MUC4)

Mucin 4 (MUC4) is a high-molecular-weight, membrane-bound glycoprotein that is aberrantly overexpressed in several aggressive cancers, particularly pancreatic ductal adenocarcinoma, while maintaining limited expression in healthy tissues (PMID: 15150590). The Major Histocompatibility Complex (MHC) peptide-binding groove presents short, processed peptides derived from the MUC4 protein on the surface of cancer cells, creating a specific target for the adaptive immune system (PMID: 15833833). This MHC-MUC4 complex is the primary ligand for T-cell receptors (TCRs) on cytotoxic T lymphocytes, making it a focal point for the development of cancer vaccines and TCR-engineered T-cell therapies (PMID: 24633177). Therapeutic strategies involve identifying immunogenic MUC4 epitopes, such as those that bind with high affinity to HLA-A*02:01, to elicit a robust and specific anti-tumor immune response. Because MUC4 plays a role in cell signaling and tumor progression, targeting its presentation on MHC molecules offers a dual advantage of immune recognition and potential disruption of oncogenic pathways. However, the success of such therapies depends on the stable presentation of these peptides and the avoidance of off-target effects in normal MUC4-expressing tissues like the respiratory tract (UniProt: Q99102).

Other names

HLA-MUC4 complexMUC4-HLA complexMucin 4 peptide-MHC complexpMHC-MUC4MUC4-derived peptide-HLA complex

Activation of antigen-specific T-cell receptors (TCRs) leading to cytotoxic T-lymphocyte (CTL) mediated lysis of tumor cells.