Receptor tyrosine-protein kinase erbB-2 (ERBB2)-derived Human leukocyte antigen A*0201 (HLA-A*0201)-restricted epitope (HER2/HLA-A*02:01 epitope)

The Receptor tyrosine-protein kinase erbB-2 (ERBB2)-derived Human leukocyte antigen A*0201 (HLA-A*0201)-restricted epitope is a specific peptide fragment from the HER2 protein presented by the MHC class I molecule HLA-A*0201 (Slingluff et al., 1994). This complex serves as a vital target for cancer immunotherapies, particularly in HLA-A2 positive patients with HER2-overexpressing tumors (Peoples et al., 2005). The most extensively studied epitope is the E75 peptide, which consists of amino acids 369–377 of the HER2 protein (Mittendorf et al., 2012). Recognition of this epitope by CD8+ cytotoxic T lymphocytes (CTLs) leads to the release of cytotoxic granules and the subsequent destruction of the cancer cell (Schmitt et al., 2009). Therapeutic strategies include peptide vaccines like Nelipepimut-S and TCR-engineered T-cell therapies designed to recognize the peptide-MHC complex (Disis et al., 2009). Unlike monoclonal antibodies that bind to the surface of the HER2 protein, these therapies target processed fragments, allowing for a different mode of immune engagement. Clinical applications are primarily focused on preventing recurrence in breast cancer patients and treating advanced HER2-positive malignancies (Gall et al., 2013). Monitoring for HLA-A*0201 expression and HER2 levels is essential for patient selection in these therapeutic contexts (Brossart et al., 1998).

Other names

HER2/HLA-A*02:01 complexE75 peptideHER2 (369-377) epitopeGP2 peptideHER2-derived pMHCERBB2-derived HLA-A*0201-restricted epitope

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