Universität zu Köln

Becker, Hans Jiro, Kondo, Eisei ORCID: 0000-0003-0995-9405, Shimabukuro-Vornhagen, Alexander ORCID: 0000-0002-2351-7294, Theurich, Sebastian ORCID: 0000-0001-5706-8258 and von Bergwelt-Baildon, Michael S. (2016). Processing and MHC class II presentation of exogenous soluble antigen involving a proteasome-dependent cytosolic pathway in CD40-activated B cells. Eur. J. Haematol., 97 (2). S. 166 - 175. HOBOKEN: WILEY. ISSN 1600-0609

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Becker, Hans Jiro UNSPECIFIED UNSPECIFIED UNSPECIFIED Kondo, Eisei UNSPECIFIED orcid.org/0000-0003-0995-9405 UNSPECIFIED Shimabukuro-Vornhagen, Alexander UNSPECIFIED orcid.org/0000-0002-2351-7294 UNSPECIFIED Theurich, Sebastian UNSPECIFIED orcid.org/0000-0001-5706-8258 UNSPECIFIED von Bergwelt-Baildon, Michael S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-267570
DOI:	10.1111/ejh.12699
Journal or Publication Title:	Eur. J. Haematol.
Volume:	97
Number:	2
Page Range:	S. 166 - 175
Date:	2016
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1600-0609
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DISTINCT PROTEOLYTIC PROCESSES; DENDRITIC CELLS; PRESENTING CELLS; T-CELLS; CROSS-PRESENTATION; IN-VIVO; LYMPHOCYTES; PEPTIDE; IMMORTALIZATION; DEGRADATION Multiple languages Hematology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26757