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T cell selection during the evolution of CD8+ T cell memory in vivo
M F Callan1, N Annels, N Steven
1Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, GB. mcallan@molbiol.ox.ac.uk
European Journal of Immunology
|December 23, 1998
Summary
Specific T cell clonotypes dominate Epstein-Barr virus (EBV) responses early in infection. These same clonotypes persist, forming the memory T cell response up to three years later, revealing early selection dynamics.
Area of Science:
- Immunology
- Virology
- T cell biology
Background:
- Memory T cell responses often exhibit restricted T cell receptor (TCR) usage.
- The mechanisms and timing of this clonotypic dominance are not fully understood.
Purpose of the Study:
- To investigate the evolution of T cell responses to a specific Epstein-Barr virus (EBV) epitope.
- To determine when and how dominant T cell clonotypes are established during primary EBV infection and memory formation.
Main Methods:
- Analysis of TCR usage in T cell clones specific for the EBV (FLRGRAYGL) epitope.
- Longitudinal sampling of peripheral blood mononuclear cells from individuals during primary EBV infection and up to 3 years post-infection.
- Utilized tetrameric MHC-peptide complexes for direct analysis of specific T cells in one case.
Main Results:
- Identified particular T cell clonotypes selected early during the primary response to the EBV epitope.
- Demonstrated that these same clonotypes constitute the dominant T cell population in the late memory response.
- Confirmed early selection of dominant clonotypes in HLA-B8-restricted T cells specific for the EBV epitope.
Conclusions:
- Clonotypic dominance in T cell responses to EBV epitopes is established early during primary infection.
- The dominant T cell clones selected early are maintained, shaping the long-term memory response.
- Understanding these selection dynamics is crucial for T cell-mediated immunity research.