Peptide-HLA-A*02:01 complex (pHLA-A*02:01)

The Peptide-HLA-A*02:01 complex is a molecular assembly consisting of a specific peptide fragment derived from tumor-associated antigens or neoantigens, the HLA-A*02:01 heavy chain, and beta-2 microglobulin. This complex is expressed on the surface of nucleated cells and serves as the primary ligand for the T-cell receptor (TCR) of CD8+ cytotoxic T cells, facilitating the recognition of non-self or altered-self proteins [PMID: 30635910]. In oncology, HLA-A*02:01 is the most frequently targeted MHC allele due to its high prevalence in the global population, particularly among Caucasians. Therapeutic agents such as TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers (e.g., ImmTACs) are designed to bind specifically to these complexes to induce a potent anti-tumor immune response [PMID: 34554117]. Notable examples include Tebentafusp, which targets a gp100 peptide, and Afamitresgene autoleucel, which targets MAGE-A4 [FDA Label, PMID: 38531254]. Clinical challenges associated with this target include the risk of off-target cross-reactivity with similar peptides in healthy tissues and the potential for tumor resistance through the loss of HLA expression [PMID: 29242357].

Other names

HLA-A*02:01-peptide complexpMHC-A*02:01Tumor antigen-HLA-A*02:01 complexMHC Class I-peptide complexpHLA-A2

Redirection of T-cells to tumor cells via high-affinity binding to the peptide-MHC complex, inducing T-cell activation and tumor cell lysis.