Human leukocyte antigen A*02 restricted tumor antigen (HLA-A*02 restricted antigen)

The HLA-A*02 restricted tumor antigen is a molecular complex consisting of the Major Histocompatibility Complex (MHC) class I molecule HLA-A*02 and a short peptide fragment derived from a tumor-associated protein. These peptides, typically 8 to 11 amino acids in length, are generated through intracellular proteolysis and transported to the cell surface to be displayed for surveillance by the immune system (UniProt P01892). Because HLA-A*02 is the most prevalent MHC class I allele in many populations, it serves as a primary scaffold for presenting intracellular tumor markers that would otherwise be invisible to traditional antibody-based therapies (NCBI PMC7044634). In the context of oncology, these complexes are targeted by advanced immunotherapies such as TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers (ImmTACs). For instance, Tebentafusp specifically targets a gp100-derived peptide presented by HLA-A*02:01, while Afamitresgene autoleucel targets MAGE-A4-derived peptides (FDA Label: Kimmtrak; FDA Label: Tecelra). These drugs work by binding the peptide-HLA complex with high affinity, thereby recruiting and activating T-cells to selectively eliminate tumor cells. The therapeutic success of this approach relies on the accurate identification of tumor-specific peptides and the patient's HLA genotype, as the interaction is highly restricted to the A*02 allele.

Other names

HLA-A2 restricted antigenMHC class I restricted tumor peptideHLA-A*02:01 restricted tumor antigenpeptide-MHC complex (pMHC)HLA-A*02/peptide complex

T-cell receptor (TCR) binding and redirection of cytotoxic T-cell activity against tumor cells presenting the specific HLA-A*02-restricted peptide. Bispecific molecules or engineered T-cells recognize the peptide-HLA complex to trigger target cell lysis.