Human epidermal growth factor receptor 2-derived peptide-MHC complex (HER2-pMHC)

Human epidermal growth factor receptor 2 (HER2/neu)-derived peptide antigens presented on Major Histocompatibility Complex (MHC) molecules are critical targets for T-cell-based cancer immunotherapies. These targets consist of specific peptide fragments, such as E75 (KIFGSLAFL) or GP2, which are generated by proteasomal degradation of the HER2 protein and subsequently loaded onto MHC Class I or II molecules for cell-surface display (Peoples et al., 2005, PMID: 16322298). Unlike traditional HER2-targeted therapies like trastuzumab that bind the extracellular domain of the intact protein, these pMHC complexes allow the immune system to see intracellularly derived signals of HER2 overexpression (Schnittger et al., 2021, PMID: 34113155). This target is primarily utilized in the development of therapeutic cancer vaccines and engineered T-cell receptor (TCR) therapies aimed at treating HER2-positive malignancies, including breast and gastric cancers (Patel et al., 2020, PMID: 33037111). However, the efficacy of these treatments is strictly dependent on the patient's HLA genotype, as specific peptides only bind to certain MHC alleles, such as HLA-A*02:01 (Greene et al., 2016, PMID: 27197066).

Other names

HER2/neu peptide-HLA complexErbB2 peptide-MHC complexHER2-derived epitopesHER2 pMHCHER2/neu-derived peptide antigens presented on MHC molecules

Induction of peptide-specific cytotoxic T-lymphocyte (CTL) or helper T-cell responses through the recognition of HER2-derived epitopes presented by MHC molecules on the surface of tumor cells (Peoples et al., 2005, PMID: 16322298).