HLA-A2-restricted T cell receptor (HLA-A2-restricted TCR)

The HLA-A2-restricted T cell receptor (TCR) is a specialized immune receptor that recognizes specific peptide fragments presented by the Human Leukocyte Antigen A2 (HLA-A2) molecule. HLA-A2 is a common MHC Class I allele, making it a primary focus for TCR-based immunotherapies (UniProt, 2024). Unlike Chimeric Antigen Receptors (CARs), these TCRs allow T cells to detect intracellular proteins that have been processed and presented on the cell surface. This recognition is highly specific to both the peptide sequence and the HLA-A2 restriction element, typically the HLA-A*02:01 subtype. In therapeutic contexts, TCRs are engineered into patient T cells (TCR-T therapy) or formatted as bispecific molecules to target cancer-testis antigens or viral proteins (FDA, 2024). Notable examples include therapies targeting MAGE-A4, NY-ESO-1, and gp100 in various malignancies like synovial sarcoma and uveal melanoma (FDA, 2022). The clinical utility of these targets is strictly limited to patients who carry the HLA-A2 genotype and whose tumors express the cognate antigen. Potential risks include cytokine release syndrome and off-target cross-reactivity with similar peptides in vital organs, which requires rigorous screening during development.

Other names

HLA-A*02-restricted T-cell receptorMHC-restricted TCRAntigen-specific T-cell receptorHLA-A2-restricted TCR

TCR-engineered T-cell therapy (TCR-T) and bispecific T-cell engagers (ImmTACs) that redirect T-cells to kill cells presenting specific peptides on HLA-A2.