Two novel squamous cell carcinoma antigen-derived HLA-A*0201-binding peptides induce in vitro and in vivo CD8+ cytotoxic T lymphocyte responses
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- Published online on: February 20, 2013 https://doi.org/10.3892/ijo.2013.1834
- Pages: 1482-1492
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Abstract
Squamous cell carcinoma antigen (SCCA) is overexpressed in many squamous cell cancers and SCCA‑derived peptide-specific CD8+ cytotoxic T lymphocytes can display cytotoxicity against tumor cells. In the present study, we screened the SCCA amino acid sequence for potential HLA-A*0201-binding CD8+ T‑cell epitopes using two predictive computational algorithms. Seven epitope candidates were selected of which SCCA246-254(llpneidgl), SCCA223-231(sledvqakv), SCCA328‑336(vlhkafvev) and SCCA324‑332(vlsgvlhka) significantly stabilized HLA-A*0201 molecules on T2 cells. Both SCCA328‑336 and SCCA324-332 induced CD8+ IFN-γ+ T‑cell responses in HLA-A*0201-positive peripheral blood mononuclear cells as assessed by intracellular cytokine staining. Consistent with this, immunization with either SCCA328-336 or SCCA324‑332 effectively elicited CD8+ IFN-γ+ T cells in HLA-A*0201 transgenic mice as visualized by IFN-γ ELISPOT assay and intracellular cytokine staining. Furthermore, CD8+ T cells induced in vitro or in vivo by SCCA328-336 or SCCA324-332 demonstrated in vitro cytotoxicity against peptide-pulsed T2 cells and splenocytes, respectively. These novel SCCA‑derived CD8+ T‑cell epitopes described, herein, may be potentially important components for diagnostic reagents and immunotherapeutic vaccines for the treatment of squamous cell carcinomas.