title: Two novel squamous cell carcinoma antigen-derived HLA-A*0201-binding peptides induce in vitro and in vivo CD8+ cytotoxic T lymphocyte responses.
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 SCCA(246-254)(llpneidgl), SCCA(223-231)(sledvqakv), SCCA(328‑336)(vlhkafvev) and SCCA(324‑332)(vlsgvlhka) significantly stabilized HLA-A*0201 molecules on T2 cells. Both SCCA(328‑336) and SCCA(324-332) 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 SCCA(328-336) or SCCA(324‑332) 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 SCCA(328-336) or SCCA(324-332) 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.
authors: Department of Microbiology and Immunology, Wenzhou Medical College, Wenzhou 325000, P.R. China.
authors: Zhi-Liang
authors: ZL
authors: Duan
authors: Zhi-Bin
authors: ZB
authors: Wang
authors: Jiang-Long
authors: JL
authors: Guo
authors: Wen-Quan
authors: WQ
authors: Liu
authors: Jun
authors: J
authors: Hu
authors: Jing
authors: J
authors: Li
authors: Si-Na
authors: SN
authors: Wang
authors: Qiang
authors: Q
authors: Li
authors: Jin-Sheng
authors: JS
authors: Wen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology*; D011485:Protein Binding; D015843:Serpins / Q000276:immunology*; D013154:Spleen / Q000166:cytology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D015843:Serpins; C051072:squamous cell carcinoma-related antigen