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The role of Tetraspanin CD63 in antigen presentation to CD4+ T cells

Petersen, Sven Hans (2011)
Ph.D. thesis, University of Birmingham.

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Abstract

CD4+ T cells play a key role in orchestrating adaptive immunity. Their activation requires antigen presentation via MHC II proteins on antigen presenting cells (APC). Exosomes are membrane vesicles released by various cell types including APCs. APC-derived exosomes are MHC class II-positive and can induce CD4+ T cell responses. MHC II delivery to the cell surface and/or exosomes might be influenced by tetraspanins, a family of transmembrane proteins. We have prepared exosomes derived from Epstein-Barr virus (EBV)-infected human B lymphoblastoid cell lines (LCLs) and shown by Western blotting and immunoelectron microscopy that they contain MHC class II and tetraspanins including CD63, CD81 and CD82. Such LCLs as well as LCL-derived exosomes can mediate immunologically specific recognition by MHC class II matched EBV antigen-specific CD4+ T cell clones when directly added to the T cells. Using shRNA, we have decreased CD63 expression in LCLs and had been studying the effect of such downregulation on LCL as well as LCL-derived exosome mediated antigen presentation. Despite an unaltered level of MHC II, CD63low LCLs showed to be hyperstimulatory. In spite of a similar depletion of CD63 in exosomes derived from CD63low LCLs, the CD4+ T cell stimulation by these exosomes was unaltered. In search for the mechanism of this phenomenon we found a higher level of exosome secretion by CD63low LCLs. We speculate that CD63 may influence T cell stimulation by exosome trafficking as well as exosome release.

Type of Work:Ph.D. thesis.
Supervisor(s):Berditchevski, Fedor
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Cancer Sciences
Subjects:R Medicine (General)
RZ Other systems of medicine
RA0421 Public health. Hygiene. Preventive Medicine
QM Human anatomy
Institution:University of Birmingham
ID Code:1709
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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