Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558213
Title: Detection and characterization of HIV-1 specific T cell responses amongst exposed and unexposed HIV-1 seronegative individuals
Author: Campion, Suzanne Lorraine
ISNI:       0000 0004 2723 0332
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2012
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Abstract:
The primary aim of this thesis was to examine whether HIV-1 specific T cell responses in HIV-1 exposed seronegative (HESN) subjects could be firstly detected and if so, conferred protection against productive infection from HIV-1. Cultured IFN-γ ELISpot found 38.7-60% of HESN subjects had detectable HIV-1 specific T cell responses. HIV-1 specific T cell responses could be titrated, were typically mediated by CD4+ T cells and tended to map to previously defined, promiscuous epitopes. In a statistically powered, retrospective study, no evidence was found to support a role for pre-existing HIV-1 specific T cell responses in either protection against or risk of HIV-1 infection. Exposure to HIV-1 impacted upon detection of pre-existing HIV-1 specific T cell responses, in terms of frequency (p=0.01), magnitude (p=0.02) and maintenance of response. This suggests, that exposure to HIV-1 was truly priming HIV-1 specific T cell responses. However, exposure to HIV-1 was not a prerequisite and HIV-1 specific T cell responses were detectable amongst HIV-1 unexposed seronegative (HUSN) donors. Similar to HESN, HIV-1 specific T cell responses detected amongst HUSN, could be mapped to the peptide level, titrated and were predominately mediated by CD4+ T cells. These T cells were shown to be detectable amongst memory CD4+ T cell subsets, suggesting they were not the result of in vitro priming. Whilst sample size was low, HIV-1 specific T cell responses, detected amongst HUSN donors were shown to be oligoclonal in TCRVβ usage. The detection of memory CD4+ HIV-1 specific T cell responses amongst HUSN opens a broader debate about the ontogeny of HIV-1 specific T cell responses, the inherent properties of the adaptive immune system and its preponderance toward degeneracy and cross reactivity. Greater understanding of these fundamental immunology questions should, improve our understanding of T cell ontogeny and hopefully prove beneficial in the design of a novel therapeutic vaccine for HIV-1.
Supervisor: McMichael, Andrew ; Goonetilleke, Nilu Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.558213  DOI: Not available
Keywords: Tropical medicine ; Immunology ; HIV/AIDS ; Medical sciences
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