論文

査読有り
2006年1月

Three immunoproteasome-associated subunits cooperatively generate a cytotoxic T-lymphocyte epitope of Epstein-Barr virus LMP2A by overcoming specific structures resistant to epitope liberation

JOURNAL OF VIROLOGY
  • Y Ito
  • ,
  • E Kondo
  • ,
  • A Demachi-Okamura
  • ,
  • Y Akatsuka
  • ,
  • K Tsujimura
  • ,
  • M Tanimoto
  • ,
  • Y Morishima
  • ,
  • T Takahashi
  • ,
  • K Kuzushima

80
2
開始ページ
883
終了ページ
890
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1128/JVI.80.2.883-890.2006
出版者・発行元
AMER SOC MICROBIOLOGY

The precise roles of gamma interferon-inducible immunoproteasome-associated molecules in generation of cytotoxic T-lymphocyte (CTL) epitopes have yet to be fully elucidated. We describe here a unique epitope derived from the Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) presented by HLA-A*2402 molecules. Generation of the epitope, designated LMP2A(222-230), from the full-length protein requires the immunoproteasome subunit low-molecular-weight protein 7 (ip-LMP7) and the proteasome activator 28-alpha subunit and is accelerated by ip-LMP2, as revealed by gene expression experiments using an LMP2A(222-230)-specific CTL clone as a responder in enzyme-linked immunospot assays. The unequivocal involvement of all three components was confirmed by RNA interference gene silencing. Interestingly, the LMP2A222-230 epitope could be efficiently generated from incomplete EBV-LMP2A fragments that were produced by puromycin treatment or gene-engineered shortened EBV-LMP2A lacking some of its hydrophobic domains. In addition, epitope generation was increased by a single amino acid substitution from leucine to alanine immediately flanking the C terminus, this being predicted by a web-accessible program to increase the cleavage strength. Taken together, the data indicate that the generation of LMP2A(222-230) is influenced not only by extrinsic factors such as immunoproteasomes but also by intrinsic factors such as the length of the EBV-LMP2A protein and proteasomal cleavage strength at specific positions in the source antigen.

Web of Science ® 被引用回数 : 10

リンク情報
DOI
https://doi.org/10.1128/JVI.80.2.883-890.2006
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000234382900034&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?eid=2-s2.0-30344445986&partnerID=MN8TOARS
URL
http://orcid.org/0000-0003-0995-9405

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