The human naive T cell repertoire is the repository of a vast array of TCRs. However, the factors that shape their hierarchical distribution and relationship with the memory repertoire remain poorly understood. In this study, we used polychromatic flow cytometry to isolate highly pure memory and naive CD8+ T cells, stringently defined with multiple phenotypic markers, and used deep sequencing to characterize corresponding portions of their respective TCR repertoires from four individuals. The extent of interindividual TCR sharing and the overlap between the memory and naive compartments within individuals were determined by TCR clonotype frequencies, such that higher-frequency clonotypes were more commonly shared between compartments and individuals. TCR clonotype frequencies were, in turn, predicted by the efficiency of their production during V (D) J recombination. Thus, convergent recombination shapes the TCR repertoire of the memory and naive T cell pools, as well as their interrelationship within and between individuals.

Although the importance of T cells in the control of infectious agents throughout the lifetime of an individual is now well established, the influence of variation within the repertoires of Ag-specific TCRs has only more recently become appreciated (1–3). Furthermore, the relative impact of the different events involved in T cell development on shaping the peripheral T cell repertoire remains poorly understood. The processes of germline V, J, and D (for β-chains) gene recombination and junctional diversification by nucleotide deletion and addition generate a vast array of> 10 18 unique TCRαβ sequences in humans; in turn, these nascent TCRs undergo thymic selection and peripheral expansion to populate the naive T cell pool, which is estimated to contain∼ 2.5× 10 7 unique TCRs (4–6). Yet, because our current understanding of T cell repertoire composition derives predominantly from studies of rather restricted epitope-specific responses, it remains unclear whether the individual clonotypes (T cell populations defined by their expressed TCRs) that make up such highly diverse naive T cell pools are equally represented to produce a featureless “repertoire landscape” or whether the distribution of clonotype sizes is quantitatively varied. If the latter is the case, the question arises as to what are the mechanisms that underlie the hierarchical features of clonotype distribution and whether any such patterns are preserved and transmitted to the memory T cell pools.