T cell selection during the evolution of CD8(+) T cell memory in vivo

Memory T cell responses are frequently highly restricted in terms of recept or usage. How and when such clonotypic dominance is established remains poo rly understood. Here we have investigated the evolution of the T cell respo nses to an epitope from Epstein-Barr virus (EBV), (FLRGRAYGL), by analyzing TCR use of clones specific for this epitope, derived from peripheral brood mononuclear cells taken from individuals early during primary EBV infectio n and up to 3 years later. We show that, in a given individual, particular T cell clonotypes are selected early during the primary response to this ep itope and that the same clonotypes dominate the late memory response. In on e individual direct analysis of HLA-B8-restricted FLRGRAYGL-specific T cell s, isolated from peripheral blood lymphocytes taken during primary EBV infe ction using a tetrameric MHC-peptide complex, confirmed the early selection of the dominant clonotypes.