Human epidermal growth factor receptor 2-derived peptide epitopes presented on major histocompatibility complex (HER2-MHC complex)

Human epidermal growth factor receptor 2 (HER2)-derived peptide epitopes presented on the major histocompatibility complex (MHC) represent a critical class of tumor-associated antigens used in cancer immunotherapy. HER2 is a proto-oncogene that is overexpressed in various malignancies, including breast, gastric, and ovarian cancers. Intracellular processing of the HER2 protein results in short peptide fragments, such as E75 (HER2 369–377) or GP2 (HER2 654–662), which are transported to the cell surface and displayed by MHC class I or II molecules (HLA in humans). These complexes are specifically recognized by the T-cell receptors (TCRs) of CD8+ or CD4+ T cells, making them ideal targets for therapeutic vaccines, TCR-engineered T-cell (TCR-T) therapies, and TCR-like antibodies. Unlike monoclonal antibodies that target the extracellular domain of the intact HER2 protein, targeting the peptide-MHC complex allows the immune system to recognize cells based on internal protein turnover and degradation, potentially overcoming resistance to traditional HER2-targeted therapies.

Other names

HER2/neu peptide-HLA complexERBB2 peptide-MHC complexHER2-derived HLA-restricted epitopesp185-derived peptide-MHC

Induction of peptide-specific cytotoxic T-lymphocyte (CTL) responses and immune-mediated lysis of HER2-expressing tumor cells.