Detection and characterization of HIV-1 specific T cell responses amongst exposed and unexposed HIV-1 seronegative individuals
<p>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.</p> <p>Cultured IFN-γ ELISpot found 38.7-60% of...
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| Format: | Thesis |
| Language: | English |
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2012
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| _version_ | 1826275148809895936 |
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| author | Campion, S |
| author2 | McMichael, A |
| author_facet | McMichael, A Campion, S |
| author_sort | Campion, S |
| collection | OXFORD |
| description | <p>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.</p> <p>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. </p> <p>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. </p> <p>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.</p> |
| first_indexed | 2024-03-06T22:54:18Z |
| format | Thesis |
| id | oxford-uuid:5fd7fca5-96bd-42c6-ac71-74c553efa2ed |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:54:18Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:5fd7fca5-96bd-42c6-ac71-74c553efa2ed2022-03-26T17:49:38ZDetection and characterization of HIV-1 specific T cell responses amongst exposed and unexposed HIV-1 seronegative individualsThesishttp://purl.org/coar/resource_type/c_db06uuid:5fd7fca5-96bd-42c6-ac71-74c553efa2edImmunologyTropical medicineMedical sciencesHIV/AIDSEnglish2012Campion, SMcMichael, AGoonetilleke, N<p>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.</p> <p>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. </p> <p>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. </p> <p>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.</p> |
| spellingShingle | Immunology Tropical medicine Medical sciences HIV/AIDS Campion, S Detection and characterization of HIV-1 specific T cell responses amongst exposed and unexposed HIV-1 seronegative individuals |
| title | Detection and characterization of HIV-1 specific T cell responses amongst exposed and unexposed HIV-1 seronegative individuals |
| title_full | Detection and characterization of HIV-1 specific T cell responses amongst exposed and unexposed HIV-1 seronegative individuals |
| title_fullStr | Detection and characterization of HIV-1 specific T cell responses amongst exposed and unexposed HIV-1 seronegative individuals |
| title_full_unstemmed | Detection and characterization of HIV-1 specific T cell responses amongst exposed and unexposed HIV-1 seronegative individuals |
| title_short | Detection and characterization of HIV-1 specific T cell responses amongst exposed and unexposed HIV-1 seronegative individuals |
| title_sort | detection and characterization of hiv 1 specific t cell responses amongst exposed and unexposed hiv 1 seronegative individuals |
| topic | Immunology Tropical medicine Medical sciences HIV/AIDS |
| work_keys_str_mv | AT campions detectionandcharacterizationofhiv1specifictcellresponsesamongstexposedandunexposedhiv1seronegativeindividuals |