Cytotoxic T lymphocyte immunodominance to Epstein-Barr virus infection

Forrest, Calum Philip Gascoyne (2017). Cytotoxic T lymphocyte immunodominance to Epstein-Barr virus infection. University of Birmingham. Ph.D.

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EBV lytic replication involves the sequential expression of a large array of antigens that potentially provides a complex antigenic challenge. Despite this number, the primary CD8+ T cell response in infectious mononucleosis (IM) patients appears focused against epitopes found in immediate-early and some early expressed antigens with responses to late antigens typically subdominant. However previous approaches have only focused on a limited number of lytic antigens. To resolve these issues, this study examines the CD8+ T cell repertoire to all EBY lytic antigens in different phases of infection.
Polyelonal CD8+ T cell lines were mitogenically expanded from IM patients or expanded in an antigenically unbiased way from post-1M patients and healthy carriers using autologous dendritic cells loaded with lysates of lytically infected cells. Target cells expressing individual lytic antigens along with donor HLA class I molecules were used to challenge polyclonal lines with responses measured by the release of IFNγ.
These studies show that the pattern of target antigen choice varies with the phase of infection and is consistent with the idea that CD8+ T cell responses in primary infection are driven by lytically infected B cells. However over time the repertoire of responses may be influenced through antigen cross-presentation.

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: Medical Research Council
Subjects: Q Science > QR Microbiology > QR355 Virology
R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)


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