Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.731925
Title: Epstein-Barr virus and multiple sclerosis : investigating EBV antigen-induced T-cell cross-recognition of central nervous system proteins
Author: Thomas, Olivia Grace
ISNI:       0000 0004 6494 8108
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2017
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Abstract:
Multiple sclerosis (MS) is a debilitating disease in which the immune system aberrantly targets the central nervous system (CNS). There is compelling evidence that Epstein-Barr virus (EBV) is associated with MS development but the pathogenic mechanisms are unknown. The molecular mimicry hypothesis suggests the immune response to EBV, which normally would restrain the virus infection, mistakenly targets CNS components. This thesis characterised humoural and cellular responses to the virus in healthy controls (HC) and MS patients, increasing the range of EBV and CNS proteins investigated and seeking evidence of crossreactivity as predicted by the hypothesis. Compared to HC, patients had elevated EBNA1 and virus capsid antigen-specific antibody responses. EBNA3-specific antibody responses were also more frequently detected in patients, a previously undescribed observation. Both groups had similar frequencies of circulating Tcells specific for autologous lymphoblastoid cell lines (LCL) or EBNA1, although minor differences in cytokine profile were detected. LCL-specific T-cell cultures established from both patients and HC exhibited cross-reactivity to CNS antigens. This result supports a role for molecular mimicry but also suggests that other unknown or more complex factors must influence MS development. While such T-cells are a necessary prerequisite for the molecular mimicry hypothesis, their presence in HC suggests other factors must influence MS development. Identification of these factors must be a priority for future studies.
Supervisor: Not available Sponsor: Multiple Sclerosis Society ; University of Birmingham
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.731925  DOI: Not available
Keywords: RC0254 Neoplasms. Tumors. Oncology (including Cancer)
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