CD8+ T-cell receptor recognizing the Nestin-derived peptide Nes2–HLA-A*02:01 complex (Nes2LR TCR)

The CD8+ T-cell receptor (TCR) recognizing the Nes2LR–MHC class I complex is a specialized immune receptor utilized in the development of adoptive cell therapies for aggressive brain tumors. This TCR specifically targets the Nes2 peptide, a nine-amino acid sequence (ILGNSLQLR) derived from the intermediate filament protein Nestin, which is presented on the cell surface by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule (Steiner et al., 2014, PMID: 25132698). Nestin is a well-known marker for neural stem cells and is significantly overexpressed in glioblastoma multiforme (GBM) and other high-grade gliomas, while remaining largely absent in mature central nervous system tissues (Dahlstrand et al., 1992, PMID: 1373974). In a therapeutic context, patient-derived T cells are engineered to express this TCR (TCR-T therapy) to selectively recognize and eliminate Nestin-positive malignant cells. Upon engagement with the Nes2–HLA-A*02:01 complex, the TCR initiates a robust cytotoxic response, including the release of perforin and granzymes, leading to tumor cell apoptosis. While this approach offers a precision medicine strategy for glioblastoma, safety challenges include the potential for off-target effects on healthy neural progenitor populations in the subventricular zone and the management of inflammatory responses within the brain.

Other names

Nestin-specific T-cell receptorNes2-specific TCRNes2-HLA-A2 TCRILGNSLQLR-specific TCRNes2-HLA-A*02:01 TCR

The TCR specifically binds to the Nes2 peptide (ILGNSLQLR) presented by the HLA-A*02:01 MHC class I molecule on tumor cells, triggering a signaling cascade through the CD3 complex that leads to T-cell activation, cytokine release, and cytotoxic lysis of the target cell.