EBV immune evasion genes modulating CD8+ T cell recognition during lytic cycle replication

Quinn, Laura (2014). EBV immune evasion genes modulating CD8+ T cell recognition during lytic cycle replication. University of Birmingham. Ph.D.

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During lytic cycle replication EBV expresses at least three genes; BNLF2a, BILF1 and BGLF5, which individually act to inhibit efficient processing and presentation of CD8+ T cell epitopes. This thesis sets out to assess the relative contribution of these potential immune-modulating proteins to the evasion from CD8+ T cells at different stages of EBV lytic cycle. Lentiviral vectors for shRNAs were used to silence expression of these individual viral genes in EBV-transformed B-cells, which were then probed with CD8+ T cell effector clones of specificities for epitopes derived from the three phases of the EBV lytic cycle; allowing us to determine the contribution each immune evasion gene makes towards the inhibition of antigen presentation during lytic cycle.
Cells replicating viruses lacking BNLF2a were more efficiently recognised by CD8+ T cells specific for immediate early and early expressed antigens relative to those lacking BGLF5 and BILF1. Conversely, cells lacking the expression of BILF1 were better recognised by CD8+ T cells specific for early and late lytic antigens. These data suggest that whilst the role BNLF2a plays in interfering with antigen presentation diminishes as lytic cycle progresses (IE>E>>L), BILF1 plays a more active role with the progression of lytic cycle (IE<E<<L).

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: Institute of Cancer Studies
Funders: None/not applicable
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
URI: http://etheses.bham.ac.uk/id/eprint/4559


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