Mucin 1 (MUC1) peptide-HLA-A*02:01 complex (MUC1/HLA-A2)

Mucin 1 (MUC1) is a high-molecular-weight transmembrane glycoprotein that is normally expressed on the apical surface of ductal epithelia but becomes overexpressed and aberrantly glycosylated in many adenocarcinomas (Source: PubMed PMID 21547901). In cancer cells, MUC1 is processed into short peptide fragments that are presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, specifically the HLA-A*02:01 allele. These HLA-A2-restricted MUC1-derived peptide epitopes, such as those derived from the signal sequence (e.g., LLLLTVLTV), serve as highly specific targets for the cellular immune system (Source: PubMed PMID 10438931). Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cells and TCR-like monoclonal antibodies, which are designed to recognize the peptide-MHC (pMHC) complex with high affinity (Source: PubMed PMID 25633478). This approach allows for the targeting of intracellularly derived MUC1 antigens that are not accessible to traditional antibodies targeting the protein's extracellular domain. Because HLA-A2 is a prevalent allele in many populations, this complex is a significant focal point for the development of precision cancer immunotherapies.

Other names

MUC1-HLA-A2 complexHLA-A*02:01-restricted MUC1 epitopeMUC1-derived peptide-MHC complexCD227-HLA-A2MUC1 pMHC

T-cell receptor (TCR) mediated recognition of the specific MUC1 peptide fragment presented within the HLA-A*02:01 groove, leading to the activation of cytotoxic T-lymphocytes (CTLs) and subsequent lysis of the target tumor cell.