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A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy
Dendritic cells (DCs) are professional antigen-presenting cells with antigen recognition molecules on the surface. Clec9a is selectively expressed on mouse CD8a(+) DCs and CD103(+) DCs subsets, which are functionally similar to human BDCA3(+) DCs. It is reported that Clec9a is responsible for the an...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130018/ https://www.ncbi.nlm.nih.gov/pubmed/27250027 http://dx.doi.org/10.18632/oncotarget.9624 |
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author | Yan, Zhongyi Wu, Yahong Du, Jiangfeng Li, Guodong Wang, Shengdian Cao, Wenpeng Zhou, Xiuman Wu, Chunjing Zhang, Dan Jing, Xueli Li, Yifan Wang, Hongfei Gao, Yanfeng Qi, Yuanming |
author_facet | Yan, Zhongyi Wu, Yahong Du, Jiangfeng Li, Guodong Wang, Shengdian Cao, Wenpeng Zhou, Xiuman Wu, Chunjing Zhang, Dan Jing, Xueli Li, Yifan Wang, Hongfei Gao, Yanfeng Qi, Yuanming |
author_sort | Yan, Zhongyi |
collection | PubMed |
description | Dendritic cells (DCs) are professional antigen-presenting cells with antigen recognition molecules on the surface. Clec9a is selectively expressed on mouse CD8a(+) DCs and CD103(+) DCs subsets, which are functionally similar to human BDCA3(+) DCs. It is reported that Clec9a is responsible for the antigen cross-presentation of these DC subsets. In the present study, by using phage display technique, we discovered a novel peptide WH, which can selectively bind to mouse Flt3L induced Clec9a(+) DCs or Clec9a over-expressed HEK-293T cells. Furthermore, by using computer-aided docking model and mutation assay, we observed that Asp(248) and Trp(250) are two key residues for Clec9a to bind with peptide WH. When coupled with OVA(257-264) epitope, peptide WH can significantly enhance the ability of Clec9a(+) DCs to activate OVA-specific CD8(+) T cells, which elicit strong ability to secret IFN-γ, express perforin and granzyme B mRNA. In B16-OVA lung metastasis mouse model, WH-OVA(257-264) fusion peptide can also enhance the activation of CD8(+) T cells and decrease the lung metastasis loci. All these results suggested that peptide WH could be considered as an antigen delivery carrier targeting Clec9a(+) DCs for cancer immunotherapy. |
format | Online Article Text |
id | pubmed-5130018 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-51300182016-12-11 A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy Yan, Zhongyi Wu, Yahong Du, Jiangfeng Li, Guodong Wang, Shengdian Cao, Wenpeng Zhou, Xiuman Wu, Chunjing Zhang, Dan Jing, Xueli Li, Yifan Wang, Hongfei Gao, Yanfeng Qi, Yuanming Oncotarget Research Paper Dendritic cells (DCs) are professional antigen-presenting cells with antigen recognition molecules on the surface. Clec9a is selectively expressed on mouse CD8a(+) DCs and CD103(+) DCs subsets, which are functionally similar to human BDCA3(+) DCs. It is reported that Clec9a is responsible for the antigen cross-presentation of these DC subsets. In the present study, by using phage display technique, we discovered a novel peptide WH, which can selectively bind to mouse Flt3L induced Clec9a(+) DCs or Clec9a over-expressed HEK-293T cells. Furthermore, by using computer-aided docking model and mutation assay, we observed that Asp(248) and Trp(250) are two key residues for Clec9a to bind with peptide WH. When coupled with OVA(257-264) epitope, peptide WH can significantly enhance the ability of Clec9a(+) DCs to activate OVA-specific CD8(+) T cells, which elicit strong ability to secret IFN-γ, express perforin and granzyme B mRNA. In B16-OVA lung metastasis mouse model, WH-OVA(257-264) fusion peptide can also enhance the activation of CD8(+) T cells and decrease the lung metastasis loci. All these results suggested that peptide WH could be considered as an antigen delivery carrier targeting Clec9a(+) DCs for cancer immunotherapy. Impact Journals LLC 2016-05-26 /pmc/articles/PMC5130018/ /pubmed/27250027 http://dx.doi.org/10.18632/oncotarget.9624 Text en Copyright: © 2016 Yan et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Yan, Zhongyi Wu, Yahong Du, Jiangfeng Li, Guodong Wang, Shengdian Cao, Wenpeng Zhou, Xiuman Wu, Chunjing Zhang, Dan Jing, Xueli Li, Yifan Wang, Hongfei Gao, Yanfeng Qi, Yuanming A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy |
title | A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy |
title_full | A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy |
title_fullStr | A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy |
title_full_unstemmed | A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy |
title_short | A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy |
title_sort | novel peptide targeting clec9a on dendritic cell for cancer immunotherapy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130018/ https://www.ncbi.nlm.nih.gov/pubmed/27250027 http://dx.doi.org/10.18632/oncotarget.9624 |
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