Human epidermal growth factor receptor 2 (HER2)-derived peptide-major histocompatibility complex class I complex (HER2-pMHC-I)

The Human epidermal growth factor receptor 2 (HER2)-derived peptide-major histocompatibility complex class I complex (HER2-pMHC-I) is a specialized antigenic target found on the surface of cells overexpressing the HER2/neu protein (PMID: 22524405). Intracellular HER2 is processed by the proteasome into short peptide fragments, such as the E75 or GP2 epitopes, which are then loaded onto MHC class I molecules (typically HLA-A*02:01) and presented on the cell surface (PMID: 21810913). These complexes are specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering an immune response against the tumor cell. This target is the focus of various immunotherapeutic strategies, including peptide vaccines like NeuVax and adoptive cell therapies using TCR-engineered T cells (TCR-T) (PMID: 31515461). Unlike traditional HER2-targeted antibodies that bind the extracellular protein domain, TCR-based therapies can target epitopes derived from any part of the HER2 protein. However, a significant challenge is the potential for on-target off-tumor toxicity, as HER2 is expressed at low levels in healthy tissues such as the heart and lungs (PMID: 20167836). Clinical development requires precise patient selection based on both HER2 expression and specific HLA typing (PMID: 25100371).

Other names

HER2-HLA complexERBB2-MHC class I complexHER2-derived peptide epitopesHER2-pMHCHER2/neu peptide-MHC complexHLA-A*02:01/HER2(369-377) complex

T-cell receptor-mediated cytotoxicity and active immunization