Identification of a New Cytotoxic T-Cell Epitope p675 of Human Telomerase Reverse Transcriptase

Abstract

Background: The identification of new tumor-associated antigens and epitopes is the prerequisite for cancer immunotherapy. The human telomerase catalytic subunit human telomerase reverse transcriptase (hTERT) is an attractive target for tumor therapy. The hTERT:540–548 peptide (p540, ILAKFLHWL) was previously identified as an HLA-A*0201-restricted T-cell epitope. However, other MHC-restricted epitopes in this antigen are urgently needed for an effective T-cell-based cancer treatment. The goal of this study was to identify other immunogenic peptides of hTERT restricted by HLA-A*0201 molecule, which accounts for about 15% of the Chinese population. Methods: Computer algorithms were used for epitope prediction, followed by analyzation on the plate of Discovery Studio 2.5. The candidate peptides were verified by T2-cell-binding assay, ELISPOT analysis, flow cytometry examination, and in vitro and in vivo tumor inhibition assay. Results: Six peptides were predicted by computer algorithms. Of these peptides, p540 and p675 (LLGASVLGL) were identified with lower binding free energies than the other four peptides, binding to HLA-A*02 more strongly, and elicited stronger IFN-γ secretion of patients' peripheral blood mononuclear cells. The CTL clone against p675 elicited a significant cancer cell inhibition effect HLA-A*0201 restrictly. Conclusions: We identified p675 as a new HLA-A*0201-restricted T-cell epitope, and the CTL clone against it could suppress tumor growth effectively.