Effects of Influenza Derived Peptide on CD8 T Cell Responses to MHC Class I-Restricted Human Telomerase Reverse Transcriptase (hTERT)-Derived Peptide

摘要

Tumor cells in breast cancer are immunogenic and express proteins that can induce immune responses. One important antigen is human telomerase reverse transcriptase (hTERT). The main aim of this study was to use an epitope from hTERT accompanied by an epitope derived from influenza virus restricted to HLA-A2, a common Class I HLA in Iran, to induce T cells against tumoral cells. The epitopes were analyzed in IEDB and EpiMHC databases for the strength of binding to HLA-A2 and immunogenicity, respectively. Peripheral blood mononuclear cells (PBMCs) from 11 HLA-A2-positive breast cancer patients were isolated and then were harvested and co-cultured with MCF-7 cells that were previously trans-loaded with synthesized peptides. PBMC proliferation, interferon- (IFN-) secretion, and activated T cell cytotoxicity were analyzed by MTT, ELISA, and LDH cytotoxicity assays, respectively. Proliferation of PBMCs incubated with the tumoral peptide was significantly greater than that of controls (P<0.001). In addition, the proliferation of PBMCs incubated with tumoral and viral peptides was greater than that of PBMCs incubated with tumoral peptide alone. The same was true of IFN- secretion and LDH release (P<0.001 and P<0.05 respectively). Tumoral peptide can induce PBMCs through a class I MHC pathway and this induction is intensified with viral peptides.