Receptor tyrosine-protein kinase erbB-2 (HER2) peptide-MHC complex (HER2 pMHC)

The HER2 (Human Epidermal Growth Factor Receptor 2) peptide-MHC complex represents a specialized therapeutic target where intracellularly processed fragments of the HER2 protein are presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules. While traditional HER2 therapies like trastuzumab target the extracellular domain of the intact protein, this target allows the immune system to recognize HER2-overexpressing cells through T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes (CTLs). This mechanism is the foundation for cancer vaccines such as Nelipepimut-S (E75) and adoptive T-cell therapies, which aim to bypass the limitations of monoclonal antibodies by leveraging the high sensitivity and specificity of the cellular immune response. HER2 is a member of the epidermal growth factor receptor family and is frequently overexpressed in various malignancies, including breast and gastric cancers, where it drives aggressive cell proliferation and survival. Targeting the HER2 pMHC complex is particularly valuable for treating tumors with lower levels of surface protein expression that may be resistant to standard antibody-based therapies, provided the patient possesses the appropriate HLA (Human Leukocyte Antigen) allele for peptide presentation (e.g., HLA-A*02:01). (Sources: PubMed: 25634695, UniProt: P04626, NIH: NCT01570036).

Other names

HER2-derived peptide-HLA complexERBB2 peptide-MHCHER2/neu peptide epitopeCD340 peptide-MHCp185erbB2 peptide-MHC

Induction of CD8+ cytotoxic T lymphocyte (CTL) response through the recognition of specific HER2-derived peptides presented by MHC Class I molecules on the surface of tumor cells.