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Title page for ETD etd-03022009-225040


Type of Document Dissertation
Author Simons, Brenna Colleen
Author's Email Address brenna.c.simons@vanderbilt.edu
URN etd-03022009-225040
Title Structural and functional determinants of effective CD8+ T cell suppression of HIV-1 replication
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Richard D'Aquila Committee Chair
Christopher Aiken Committee Member
claudio mosse Committee Member
Luc Van Kaer Committee Member
Spyros Kalams Committee Member
Keywords
  • T cell
  • CD8
  • immunology
  • HIV (Viruses) -- Reproduction
  • T cells -- Receptors
  • CD antigens
Date of Defense 2009-02-13
Availability unrestricted
Abstract
CD8+ T cells are a critical component of an HIV-specific immune response. Our studies aimed to define the T cell receptor (TCR) structural determinants as well as effector functions associated with CD8+ T cell suppression of HIV replication. We demonstrate biased gene usage in dominant HIV epitope-specific TCR repertoires during chronic HIV infection. Despite this evidence for convergent evolution to a highly conserved viral epitope, our results indicate TCR diversity can still provide the structural ability to recognize viral variants. To better understand the role of proliferative capacity in CD8+ T cell-mediated suppression of HIV replication, we directly assessed proliferation and suppression simultaneously in vitro. We found that low proliferating CD8+ T cells suppressed HIV replication in vitro similar to levels of suppression of high-proliferating CD8+ T cells. Our data also revealed low-proliferating cells to have higher frequencies of HIV-specific IFN+TNF+ T cells. These results suggest a critical role for remaining effector functions in the absence of proliferation. Together our findings have implications for improved assessment of candidate HIV vaccine elicited immune responses and further investigations into the correlates of control of HIV-1 viremia.
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