2009年4月
Enhanced generation of cytotoxic T lymphocytes by increased cytosolic delivery of MHC class I epitope fused to mouse heat shock protein 70 via polyhistidine conjugation
JOURNAL OF CONTROLLED RELEASE
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- 巻
- 135
- 号
- 1
- 開始ページ
- 11
- 終了ページ
- 18
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.jconrel.2008.11.024
- 出版者・発行元
- ELSEVIER SCIENCE BV
Heat shock protein 70 (Hsp70)-associated antigens in a soluble form have been shown to elicit strong antigen-specific cytotoxic T lymphocyte (CTL) responses following immunization without any adjuvants. In order to improve the potential of Hsp70, we genetically designed a novel Hsp70-based antigen delivery system, in which the model MHC class I epitope of ovalbumin (OVA) (SIINFEKL; OVA257-264) was fused to mouse Hsp70. To facilitate the cytosolic delivery of the peptide following Hsp receptor-mediated endocytosis, polyhistidine of 25 or 50 residues was further fused to the fusion protein. Each fusion protein was then expressed in E. coli and purified. When added to DC2.4 cells, a mouse dendritic cell line, the fusion protein containing polyhistidine of 25 residues was efficiently taken up by the cells and efficiently distributed to the cytosol. The fusion protein also exhibited a significantly improved efficacy of MHC class I-restricted presentation of antigen. Vaccination of mice with the polyhistidine fusion protein generated strong antigen-specific CTL responses and antitumor activity. These findings suggest that polyhistidine fusion is a useful strategy to increase the potential of Hsp-based vaccination. (C) 2008 Elsevier B.V. All rights reserved.
- リンク情報
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- DOI
- https://doi.org/10.1016/j.jconrel.2008.11.024
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902205937225230
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/19100299
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000264963500003&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1016/j.jconrel.2008.11.024
- ISSN : 0168-3659
- eISSN : 1873-4995
- J-Global ID : 200902205937225230
- PubMed ID : 19100299
- Web of Science ID : WOS:000264963500003