論文

査読有り
2016年8月

Processing and MHC class II presentation of exogenous soluble antigen involving a proteasome-dependent cytosolic pathway in CD40-activated B cells

EUROPEAN JOURNAL OF HAEMATOLOGY
  • Hans Jiro Becker
  • ,
  • Eisei Kondo
  • ,
  • Alexander Shimabukuro-Vornhagen
  • ,
  • Sebastian Theurich
  • ,
  • Michael S. von Bergwelt-Baildon

97
2
開始ページ
166
終了ページ
174
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/ejh.12699
出版者・発行元
WILEY-BLACKWELL

Activated B cells have the capacity to present antigen and induce immune responses as potent antigen-presenting cells (APCs). As in other APCs, antigen presentation by B cells involves antigen internalization, antigen processing, and peptide loading onto MHC molecules. However, while the mechanism of antigen processing has been studied extensively in other APCs, this pathway remains elusive in B cells. The aim of this study was to investigate the MHC class II processing pathway in CD40-activated B cells (CD40Bs), as a model for activated, antigen-presenting B cells. Using CMV pp65 as a model antigen, we evaluated processing and presentation of the CD4 + T-cell epitope 509-523 (K509) by human CD40Bs in ELISPOT assays. As expected, stimulation of specific CD4 + T-cell clones was attenuated after pretreatment of CD40Bs with inhibitors of classic class II pathway components. However, proteasome inhibitors such as epoxomicin limited antigen presentation as well. This suggests that the antigen is processed in a non-classical, cytosolic MHC class II pathway. Further experiments with truncated protein variants revealed involvement of the proteasome in processing of the N and C extensions of the epitope. Access to the cytosol was shown to be size dependent. Epoxomicin sensitivity exclusively in CD40B cells, but not in dendritic cells, suggests a novel processing mechanism unique to this APC. Our data suggest that B cells process antigen using a distinct, non-classical class II pathway.

Web of Science ® 被引用回数 : 6

リンク情報
DOI
https://doi.org/10.1111/ejh.12699
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000383470000008&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?eid=2-s2.0-84978138309&partnerID=MN8TOARS
URL
http://orcid.org/0000-0003-0995-9405

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