Urea-Mediated Cross-Presentation of Soluble Epstein-Barr Virus BZLF1 Protein

Barabas, Sascha and Gary, Regina and Bauer, Tanja and Lindner, Juha and Lindner, Petra and Weinberger, Birgit and Jilg, Wolfgang and Wolf, Hans and Deml, Ludwig (2008) Urea-Mediated Cross-Presentation of Soluble Epstein-Barr Virus BZLF1 Protein. PLOS PATHOGENS, 4 (11): e1000198. ISSN 1553-7366,

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Abstract

Soluble extracellular proteins usually do not enter the endogenous human leukocyte antigen (HLA) I-dependent presentation pathway of antigen-presenting cells, strictly impeding their applicability for the re-stimulation of protein-specific CD8(+) cytotoxic T lymphocytes (CTL). Here we present for the Epstein-Barr virus (EBV) BZLF1 a novel strategy that facilitates protein translocation into antigen-presenting cells by its solubilisation in high molar urea and subsequent pulsing of cells in presence of low molar urea. Stimulation of PBMC from HLA-matched EBV-seropositive individuals with urea-treated BZLF1 but not untreated BZLF1 induces an efficient reactivation of BZLF1-specific CTL. Urea-treated BZLF1 (uBZLF1) enters antigen-presenting cells in a temperature-dependent manner by clathrin-mediated endocytosis and is processed by the proteasome into peptides that are bound to nascent HLA I molecules. Dendritic cells and monocytes but also B cells can cross-present uBZLF1 in vitro. The strategy described here has potential for use in the development of improved technologies for the monitoring of protein-specific CTL.

Item Type: Article
Uncontrolled Keywords: CLASS-I PRESENTATION; T-CELL RESPONSES; TAT-FUSION PROTEINS; DENDRITIC CELLS; EXOGENOUS ANTIGEN; ADAPTIVE IMMUNITY; NUCLEAR ANTIGEN; TRANSDUCTION; LYMPHOCYTES; MOLECULES;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Depositing User: Dr. Gernot Deinzer
Date Deposited: 21 Oct 2020 08:26
Last Modified: 21 Oct 2020 08:26
URI: https://pred.uni-regensburg.de/id/eprint/30141

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