Factors affecting CD4 T cell recognition of the EBV-encoded tumour antigen EBNA1

Leonard, Henry (2014). Factors affecting CD4 T cell recognition of the EBV-encoded tumour antigen EBNA1. University of Birmingham. M.Res.

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Abstract

Epstein-Barr virus (EBV) is associated with 200,000 cases of cancer per year. Although these include B cell lymphomas and epithelial carcinomas, the ability of T cells specific to viral antigens to target the latter, which constitute the majority of cases, has not been explored. In this study I have investigated the processing and CD4 T cell recognition of epithelial cells expressing EBNA1, a virally-encoded protein expressed in all EBV-associated malignancies. EBNA1 was equally stable in B cells and epithelial cells but EBNA1-specific CD4 T cell clones were nevertheless able to recognise both types of target cell. The potential effects of EBV-encoded micro-RNA BART18 on autophagy and CD4 T cell recognition were examined and showed that the loss of BART18 increased the autophagy levels of EBV-positive Jijoye Burkitt lymphoma cells under nutrient starvation conditions. Finally, the effects of a pharmacological inhibitor of EBNA1 dimerisation, JLP2, on the viability and T cell recognition of EBV-positive B cells was also investigated. JLP2 did not increase CD4 T cell recognition but transiently decreased the viability of one of two EBV-positive lymphoblastoid cell lines coincident with this line’s uptake of the drug.

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

Supervisor(s):