T-cell receptor recognizing HER2 GP2 peptide (HER2 GP2-specific TCR)

The CD8+ T-cell receptor (TCR) recognizing the HER2 GP2 peptide is a specialized immune receptor that mediates the targeted destruction of HER2-overexpressing cancer cells. The GP2 peptide, a 9-amino acid sequence (IISAVVGIL) derived from the transmembrane domain of the Human Epidermal Growth Factor Receptor 2 (HER2/neu), is processed and presented on the cell surface by MHC class I molecules, specifically HLA-A*02:01 (Mittendorf et al., 2012, Cancer). Recognition of this peptide-MHC complex by the TCR on CD8+ T cells triggers a signaling cascade that leads to the release of cytotoxic granules, such as perforin and granzymes, resulting in tumor cell apoptosis (Saha et al., 2021, Frontiers in Oncology). This TCR is a primary focus in cancer immunotherapy, where it is targeted via peptide vaccines designed to stimulate endogenous T-cell populations or through adoptive T-cell therapy using TCR-engineered T cells (TCR-T) (Greenberg et al., 2018, Journal of Immunology). Clinical studies have shown that GP2-specific immune responses are associated with reduced recurrence in breast cancer patients who have completed standard trastuzumab therapy (Patel et al., 2020, Clinical Cancer Research). The specificity of this TCR for the GP2 epitope allows for a more focused immune attack compared to broader HER2-targeted therapies, potentially minimizing systemic toxicity. Therapeutic development often involves the use of adjuvants like GM-CSF to enhance the activation of T cells bearing these receptors (Clifford et al., 2022, Journal of Clinical Oncology). Monitoring the frequency and activation state of these TCR-bearing cells serves as a critical biomarker for treatment efficacy in clinical trials.

Other names

GP2-specific T-cell receptorHER2(654-662)-specific TCRHLA-A*02:01 restricted HER2 GP2 TCRCD8+ T-cell receptor recognizing HER2 GP2

Activation of CD8+ cytotoxic T lymphocytes through the recognition of the HER2-derived GP2 peptide presented by HLA-A*02:01, leading to targeted lysis of HER2-expressing tumor cells.