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Identification of dengue virus-derived highly conserved HLA-A*1101-restricted T-cell epitopes and study on their in vivo immune responses |
CHEN Xinyu1, DUAN Zhiliang1, JIANG Minghua1, JIA Qingjun2, XU Juanjuan2, CHEN Bokun2, WEN Jinsheng1,2. |
1.Department of Clinical Laboratory, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027; 2.Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035 |
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Cite this article: |
CHEN Xinyu,DUAN Zhiliang,JIANG Minghua, et al. Identification of dengue virus-derived highly conserved HLA-A*1101-restricted T-cell epitopes and study on their in vivo immune responses[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2016, 46(8): 554-560.
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Abstract Objective: To identify dengue virus serotype 2 (DENV-2)-derived HLA-A*1101-restricted T-cell epitopes and explore the characteristics of induced T cells. Methods: Based on the complete amino acid sequence of DENV-2, T-cell epitope prediction software was utilized to predict putative HLA-A*1101-restricted T-cell epitope. Based on HLA-A*1101 transgenic mice, the HLA-A*1101 restriction of epitope candidates and the characteristics of induced T cells were determined using ELISPOT assay, ELISA assay and CTL cytotoxicity assay. Results: Among 14 epitope candidated, each of 9 peptide (NS1161-170, NS1263-272, NS36-15, NS4b44-53, NS333-42, C58-67, E30-38, NS3576-584, and NS4a72-80) could induce IFN-γ-secreting T cell response in HLA-A*1101 transgenic mice. Except for IFN-γ, C58-67 - and NS3576-584 -specific T cells also could secret TNF-α while E30-38-specific T cells could secret TNF-α and IL-6 simultaneously. High levels of IFN-γ-secreting T cells were detected in DENV-2-infected HLA-A*1101 transgenic mice and directed to 6 peptides (NS4b44-53, NS333-42, C58-67, E30-38, NS3576-584, and NS4a72-80). The effector cells from HLA-A*1101 transgenic mice immunized with the mixture of 6 above-mentioned peptides efficiently lysed DENV-2-infected splenic monocytes. Conclusion: Nine DENV-2-derived peptides are identified as HLA-A*1101-restricted T-cell epitopes.
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Received: 11 November 2015
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