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Title: T cell quality in HIV infection
Author: Hickling, Stephen J.
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2010
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The tempo of HIV disease progression might rest with particular characteristics of certain HLA class I molecules, and the CD8+ T cell populations, which they dictate. Therefore we wanted to investigate if CD8+ T cell quality in HIV infection determines disease progression. To do this we used patients recruited from the UK arm of the SPARTAC clinical trial (n=155) that were acute (seroconverted within the previous 2 months, n=5) or early infected (seroconverted within the previous 6 months, n=150). These patients were followed into chronic infection (infected for 1 year, n= 117). To determine CD8+ T cell quality we developed novel HLA class I CD8null tetramers, which allow direct detection of high avidity CD8+ HIV -specific T cells ex vivo. Furthermore, by FACS analysis we analysed high and low avidity HIV -specific T cell T EMRA lineage differentiation (populations defined by CCR7, CD45RA and CD27) and T cell exhaustion (defined by PD-l, TIM-3 and LAG-3 expression). We show that high avidity HIV- specific T cells are present in both early and chronic HIV infection. A significantly greater proportion of CD8+ HIV -specific T cell populations restricted by HLA-B molecules are high avidity in comparison to HLA-A restricted populations (p
Supervisor: Phillips, Rodney Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available