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The HLA-A*24:02-presented human telomerase reverse transcriptase (hTERT) 324-332 peptide complex is a specific tumor-associated antigen complex found on the surface of malignant cells. It consists of the nonameric peptide VYAETKHFL, derived from the catalytic subunit of telomerase, bound within the groove of the HLA-A*24:02 major histocompatibility complex (MHC) class I molecule (Akiyama et al., 2002, Cancer Immunol Immunother). Telomerase is an ideal target for cancer immunotherapy because it is overexpressed in approximately 90% of all human cancers to facilitate replicative immortality, while its expression is highly restricted in normal adult somatic tissues (Mizukoshi et al., 2006, J Immunol). The HLA-A*24:02 allele is particularly prevalent in East Asian populations, making this specific complex a high-priority target for regional precision medicine. Therapeutic interventions targeting this complex, such as TCR-engineered T-cell (TCR-T) therapies and peptide vaccines, aim to harness the immune system to recognize and destroy hTERT-positive tumor cells. Upon recognition by a cognate T-cell receptor, the complex triggers a signaling cascade that results in the release of cytotoxic granules, such as perforin and granzymes, inducing apoptosis in the target cell.
T-cell receptor (TCR) mediated recognition of the pMHC complex leading to cytotoxic T-lymphocyte (CTL) activation and tumor cell lysis.
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