HLA-A*24:02-peptide-specific T-cell receptor complex (HLA-A*24:02-TCR complex)

The HLA-A*24:02-peptide-specific T-cell receptor complex is a molecular assembly consisting of a specific peptide antigen presented by the Human Leukocyte Antigen (HLA) allele A*24:02 and its cognate T-cell receptor (TCR). HLA-A*24:02 is a Class I MHC molecule highly prevalent in East Asian populations, making it a critical target for precision immunotherapy in these regions (Gonzalez-Galarza et al., 2020). This complex is the primary recognition unit for CD8+ T cells, which monitor the intracellular proteome for viral or oncogenic transformations. In a therapeutic context, this complex is targeted by TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers designed to recognize tumor-associated antigens such as NY-ESO-1, WT1, or MAGE-A4 (Ochi et al., 2011). Upon binding, the therapeutic TCR triggers a signaling cascade that results in the formation of an immunological synapse, cytokine secretion, and the direct lysis of the target cell (D'Angelo et al., 2018). Clinical development focusing on this target is particularly relevant for treating solid tumors and hematological malignancies in patients carrying the A*24:02 allele. However, the high specificity required for TCR binding poses challenges, including the risk of off-target cross-reactivity with similar self-peptides found in healthy tissues (Linette et al., 2013). Successful engagement of this target requires both the presence of the HLA-A*24:02 allele and the sufficient expression of the specific intracellular antigen.

Other names

HLA-A24-restricted TCRpMHC-TCR complex (HLA-A*24:02)HLA-A*24:02-antigen-TCR complexHLA-A*24:02-peptide-TCR

Therapeutic TCRs or TCR-engineered T-cells bind specifically to the peptide-HLA-A*24:02 complex on target cells, inducing immunological synapse formation and subsequent T-cell mediated cytotoxicity (Nature Reviews Cancer, 2021).