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Title: The role of Tetraspanin CD63 in antigen presentation to CD4+ T cells
Author: Petersen, Sven Hans
ISNI:       0000 0004 2700 1142
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2011
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: R Medicine (General) ; RZ Other systems of medicine ; RA0421 Public health. Hygiene. Preventive Medicine ; QM Human anatomy