Islam SA, Cohen GB, Noble M, Lau C, He S, Altfeld MA, Rosenberg E, Walker BD, Kalams SA.
AIDS Vaccine 2001. 2001 Sep 5-8; abstract no. 34.
Partners AIDS Res. Ctr. and Infectious Disease Unit, Massachusetts Gen. Hosp., and Harvard Med. Sch., Boston, MA, USA
BACKGROUND: The generation of diverse TCR repertoires to immunodominant viral epitopes after acute infections is likely to be important for control of viremia and establishment of viral set point, and the ability to induce these responses will be an important property of a successful HIV vaccine.METHODS: We sorted populations of live antigen-specific T cells relying on surface capture of IFN-gamma after antigenic stimulation, followed by TCR repertoire analysis of the sorted cells, and applied these methods to the study of EBV and HIV-1 infection.RESULTS: We evaluated the TCR repertoire of cells specific for an immunodominant A2.01-restricted lytic cycle epitope in 2 subjects with chronic EBV infection. We found that although the frequency of tetramer-positive cells was 2- to 4-fold higher than the frequency of the IFN-gamma secreting cells, the TCR repertoires of the 2 populations were nearly identical. Therefore, factors outside of the sequence of the TCR must account for the differential ability of a T cell to produce IFN-gamma. In HIV-1 infection we studied the immunodominant HLA B14-restricted Env EL9 response. T cells that recognized this epitope werepolyclonal yet contained a highly conserved GQG motif derived from D?1 germline DNA in the CDR3 region. We speculate that many naive T cells contain this motif and that a high frequency of precursor cells may account for the immunodominance of this epitope during acute HIV-1 infection. We also provide evidencethat despite the polyclonal T-cell response against this epitope, the T cells that recognize this epitope have a limited ability to recognize other naturally occurring HIV-1 variants of this epitope.CONCLUSIONS: Longitudinal studies of these responses over the course of HIV-1 infection will allow us to understand the dynamics of the TCR repertoire and its relation to the establishment of viral set point. Understanding these dynamics and the role that broadly reactive T cells may play in limiting viral escape variants may have important implications for HIV-1 vaccine design.
Publication Types:
Keywords:
- AIDS Vaccines
- Epitopes
- Epstein-Barr Virus Infections
- HIV Infections
- HIV-1
- Herpesvirus 4, Human
- Immunodominant Epitopes
- Longitudinal Studies
- Receptors, Antigen, T-Cell
- T-Lymphocytes
- immunology
Other ID:
UI: 102249278
From Meeting Abstracts