HLA-A*02:01-restricted T-cell receptor (HLA-A2-restricted TCR)

The T-cell receptor (TCR) on CD8+ T cells is a specialized heterodimeric surface protein responsible for recognizing intracellular antigens presented as short peptides by Major Histocompatibility Complex (MHC) class I molecules. Specifically, TCRs restricted to the HLA-A*02:01 allele are of significant therapeutic interest because HLA-A*02:01 is one of the most prevalent MHC alleles in Western populations and frequently presents peptides derived from tumor-associated antigens (TAAs) or neoantigens. In cancer immunotherapy, these TCRs are utilized in two primary formats: adoptive TCR-engineered T-cell (TCR-T) therapies, where a patient's own T cells are modified to express a tumor-specific TCR, and bispecific TCR-based engagers, which bridge T cells to tumor cells. These therapies aim to induce targeted cytotoxicity and tumor regression by exploiting the high sensitivity of the TCR for its cognate peptide-HLA complex. However, clinical application is challenged by the risk of off-target cross-reactivity with self-peptides and the requirement for precise HLA matching between the therapy and the patient.

Other names

HLA-A*02:01-restricted T-cell receptorHLA-A2-restricted TCRTumor-specific T-cell receptorEngineered T-cell receptorTCR restricted to HLA-A*02:01

Redirection of T-cell cytotoxicity toward tumor cells via recognition of specific peptide-HLA complexes. For TCR-T therapies, this involves ex vivo engineering of T cells to express a specific TCR. For bispecifics, it involves simultaneous binding of the TCR domain to the tumor pHLA complex and the CD3 domain to T cells, inducing an immunological synapse.