T cell receptor recognizing peptide–HLA-A*2402 complexes (TCR/pHLA-A*24:02)

The T cell receptor (TCR) on CD8+ cytotoxic T lymphocytes (CTLs) is a heterodimeric protein complex, typically composed of alpha (TRAC) and beta (TRBC) chains, that recognizes specific antigenic peptides presented by the Major Histocompatibility Complex (MHC) Class I molecule HLA-A*24:02 (UniProt P01892; IMGT/HLA) [1]. HLA-A*24:02 is a highly prevalent allele in East Asian populations, making it a critical restriction element for the presentation of tumor-associated antigens (TAAs) such as WT1, MAGE-A4, and NY-ESO-1 [2][3]. Upon binding to the peptide-HLA-A*24:02 complex, the TCR triggers a signaling cascade through the CD3 complex, leading to T-cell activation, proliferation, and the release of cytotoxic granules like perforin and granzymes to eliminate the target cell [4]. This specific recognition mechanism is the foundation for TCR-engineered T-cell (TCR-T) therapies, which involve modifying a patient's T cells to express a TCR specific for a tumor antigen presented by HLA-A*24:02 [5]. Therapeutic development in this area aims to achieve high affinity for the target complex while avoiding cross-reactivity with similar peptides in healthy tissues, which can cause severe off-target toxicity [6]. Clinical efficacy is often monitored through biomarkers such as HLA-A*24:02 genotype and the expression levels of the target antigen within the tumor microenvironment [7].

Other names

HLA-A*24:02-restricted T-cell receptorA24-restricted TCRAntigen-specific TCRCD8+ T-lymphocyte receptorT-cell receptor alpha/beta

Engineered or endogenous TCRs bind specifically to peptide-HLA-A*24:02 complexes on the surface of target cells, inducing T-cell activation and directed lysis of the target cell via the release of cytotoxic molecules.