Human epidermal growth factor receptor 2 – Human leukocyte antigen A*02 peptide complex (HER2-HLA-A2)

The Human epidermal growth factor receptor 2 – Human leukocyte antigen A*02 (HER2-HLA-A2) peptide complex is a cell-surface antigen formed when intracellularly processed HER2 protein fragments are loaded onto HLA-A*02 MHC class I molecules for presentation to the immune system (Mittendorf et al., 2012, Cancer). This complex is a critical target in cancer immunotherapy, particularly for patients with HER2-positive or HER2-low tumors who also carry the HLA-A*02 allele, which is present in approximately 40-50% of the Caucasian population (Gonzalez-Galarza et al., 2020, Nucleic Acids Res). The biological function of this complex is to signal the presence of abnormal or overexpressed proteins to CD8+ cytotoxic T lymphocytes (CTLs), triggering an adaptive immune response (Peoples et al., 2005, J Clin Oncol). In many cancers, including breast, ovarian, and gastric carcinomas, the overabundance of this complex makes it a highly specific marker for malignant cells (Disis et al., 2009, Clin Cancer Res). Therapeutic strategies targeting this complex include peptide vaccines such as Nelipepimut-S (E75) and GP2, which prime the patient's immune system to recognize the complex, as well as engineered T-cell receptor (TCR) therapies and TCR-like antibodies (Brown et al., 2020, Breast Cancer Res Treat). These treatments aim to induce direct lysis of tumor cells and establish long-term immunological memory to prevent disease recurrence (Lowenfeld et al., 2014, OncoImmunology).

Other names

HER2/neu-HLA-A*02:01 complexp95HER2/HLA-A2 complexE75-HLA-A2 complexGP2-HLA-A2 complexHER2 peptide-MHC complex

Induction of CD8+ cytotoxic T lymphocyte-mediated lysis of HER2-expressing cells through specific recognition of the HER2 peptide-HLA-A2 complex.