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Processing and MHC class II presentation of exogenous soluble antigen involving a proteasome‐dependent cytosolic pathway in CD 40‐activated B cells
Author(s) -
Becker Hans Jiro,
Kondo Eisei,
ShimabukuroVornhagen Alexander,
Theurich Sebastian,
BergweltBaildon Michael S.
Publication year - 2016
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12699
Subject(s) - antigen processing , antigen presentation , antigen , antigen presenting cell , mhc class i , epitope , biology , microbiology and biotechnology , cytotoxic t cell , major histocompatibility complex , t cell , transporter associated with antigen processing , immune system , immunology , biochemistry , in vitro
Abstract Activated B cells have the capacity to present antigen and induce immune responses as potent antigen‐presenting cells ( APC s). As in other APC s, 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 APC s, this pathway remains elusive in B cells. The aim of this study was to investigate the MHC class II processing pathway in CD 40‐activated B cells ( CD 40Bs), as a model for activated, antigen‐presenting B cells. Using CMV pp65 as a model antigen, we evaluated processing and presentation of the CD 4 + T‐cell epitope 509‐523 (K509) by human CD 40Bs in ELISPOT assays. As expected, stimulation of specific CD 4 + T‐cell clones was attenuated after pretreatment of CD 40Bs 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 CD 40B 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.