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A Mechanism for TCR Sharing between T Cell Subsets and Individuals Revealed by Pyrosequencing

2011; American Association of Immunologists; Volume: 186; Issue: 7 Linguagem: Inglês

10.4049/jimmunol.1003898

1550-6606

Vanessa Venturi, Máire F. Quigley, Hui Yee Greenaway, Pauline C. Ng, Zachary Ende, Tina C. McIntosh, Tedi E. Asher, Jorge R. Almeida, Samuel Lévy, David A. Price, Miles P. Davenport, Daniel C. Douek,

Immune Cell Function and Interaction

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.