title: Cathepsin E regulates the presentation of tetanus toxin C-fragment in PMA activated primary human B cells.
abstract: Processing of antigens by proteases in the endocytic compartments of antigen presenting cells (APC) is essential to make them suitable for presentation as antigenic peptides to T lymphocytes. Several proteases of the cysteine, aspartyl and serine classes are involved in this process. It has been speculated, that the aspartyl protease cathepsin E (CatE) is involved in antigen processing in B cell line, monocyte-derived dendritic cells (DC) and murine DC. Here we show the expression of CatE in primary human B cells and DC, which was only elevated in B cells after induction with phorbol 12-myristate 13-acetate (PMA), resulted in enhanced presentation of tetanus toxin C-fragment (TTC) to the respective T cells. Inhibition of aspartyl proteases using pepstatin-A-penetratin (PepA-P), a highly efficient, cell-permeable aspartyl protease inhibitor, reduced significantly T cell activation in PMA activated B cells but not in PMA activated myeloid DC (mDC). Thus we suggest that CatE is important in the processing of TTC in primary human B cells.
authors.affiliation: Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Medical Center Ulm, Robert-Koch-Str. 8, Ulm, Germany. tburster@stanford.edu
authors.forename: Timo
authors.initials: T
authors.lastname: Burster
authors.forename: Michael
authors.initials: M
authors.lastname: Reich
authors.forename: Nousheen
authors.initials: N
authors.lastname: Zaidi
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voelter
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Boehm
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
mesh_terms: D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D020059:Cathepsin E / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D010436:Pepstatins / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D013744:Tetanus Toxin / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D010436:Pepstatins; D010446:Peptide Fragments; D013744:Tetanus Toxin; C040635:tetanus toxin fragment C; D020059:Cathepsin E; D013755:Tetradecanoylphorbol Acetate; C031375:pepstatin