T-cell receptor–HLA-A*02:01–GP2 peptide complex (TCR-HLA-A*02:01-GP2)

The T-cell receptor–HLA-A*02:01–GP2 peptide complex is a molecular assembly critical for the targeted immune recognition of HER2/neu-expressing cancer cells (Mittendorf et al., 2014, Cancer). The GP2 peptide, a 9-amino acid sequence (IISAVVGIL) derived from the transmembrane domain of the HER2/neu protein, is presented by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule on the surface of tumor cells (Peoples et al., 1995, PNAS). This peptide-MHC complex is specifically recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, triggering an immune response and subsequent cell lysis (Greenwich LifeSciences, 2024). This interaction is the primary target for therapeutic strategies such as the GP2 vaccine (GLSI-100) and TCR-engineered T-cell therapies, which aim to enhance the body's ability to eliminate residual disease in HER2-positive cancers (Saha et al., 2021, Frontiers in Oncology). By focusing on this specific complex, therapies can achieve high specificity for malignant cells while minimizing damage to healthy tissues that do not overexpress HER2. Clinical studies have demonstrated that targeting this complex can significantly reduce recurrence rates in breast cancer patients who have completed standard trastuzumab therapy (Patel et al., 2020, SABCS).

Other names

HER2 GP2-HLA-A*02:01 complexTCR-pMHC (GP2) complexHER2/neu peptide GP2-MHC complexGP2-HLA-A2 complex

Induction of peptide-specific cytotoxic T-lymphocyte (CTL) responses against HER2/neu-expressing cells through the recognition of the GP2 peptide presented by HLA-A*02:01 (Mittendorf et al., 2014, Cancer).