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Convergent recombination shapes the clonotypic landscape of the naive T-cell repertoire

Quigley, Maire F., Greenaway, Hui Yee, Venturi, Vanessa, Lindsay, Ross, Quinn, Kylie M., Seder, Robert A., Douek, Daniel C., Davenport, Miles P. and Price, David 2010. Convergent recombination shapes the clonotypic landscape of the naive T-cell repertoire. Proceedings of the National Academy of Sciences of the United States of America 107 (45) , pp. 19414-19419. 10.1073/pnas.1010586107

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Abstract

Adaptive T-cell immunity relies on the recruitment of antigen-specific clonotypes, each defined by the expression of a distinct T-cell receptor (TCR), from an array of naïve T-cell precursors. Despite the enormous clonotypic diversity that resides within the naïve T-cell pool, interindividual sharing of TCR sequences has been observed within mobilized T-cell responses specific for certain peptide–major histocompatibility complex (pMHC) antigens. The mechanisms that underlie this phenomenon have not been fully elucidated, however. A mechanism of convergent recombination has been proposed to account for the occurrence of shared, or “public,” TCRs in specific memory T-cell populations. According to this model, TCR sharing between individuals is directly related to TCR production frequency; this, in turn, is determined on a probabilistic basis by the relative generation efficiency of particular nucleotide and amino acid sequences during the recombination process. Here, we tested the key predictions of convergent recombination in a comprehensive evaluation of the naïve CD8+ TCRβ repertoire in mice. Within defined segments of the naïve CD8+ T-cell repertoire, TCRβ sequences with convergent features were (i) present at higher copy numbers within individual mice and (ii) shared between individual mice. Thus, the naïve CD8+ T-cell repertoire is not flat, but comprises a hierarchy of recurrence rates for individual clonotypes that is determined by relative production frequencies. These findings provide a framework for understanding the early mobilization of public CD8+ T-cell clonotypes, which can exert profound biological effects during acute infectious processes.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > R Medicine (General)
Publisher: National Academy of Sciences
ISSN: 0027-8424
Last Modified: 04 Jun 2017 03:42
URI: http://orca-mwe.cf.ac.uk/id/eprint/25207

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