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

Máire F. Quigley, Hui Yee Greenaway, Vanessa Venturi, Ross Lindsay, Kylie M. Quinn, Robert A. Seder, Daniel C. Douek, Miles P. Davenport, David A. Price

Research output: Contribution to journalArticleResearchpeer-review

89 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)19414-19419
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number45
DOIs
Publication statusPublished - 9 Nov 2010
Externally publishedYes

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