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Proceedings of the National Academy of Sciences
Article . 2010 . Peer-reviewed
Data sources: Crossref
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Convergent recombination shapes the clonotypic landscape of the naïve T-cell repertoire

Authors: Máire F, Quigley; Hui Yee, Greenaway; Vanessa, Venturi; Ross, Lindsay; Kylie M, Quinn; Robert A, Seder; Daniel C, Douek; +2 Authors

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

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.

Keywords

Recombination, Genetic, Mice, T-Lymphocytes, Genes, T-Cell Receptor beta, Animals, Adaptive Immunity, CD8-Positive T-Lymphocytes, Clone Cells

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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    113
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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
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    impulse
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    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
113
Top 10%
Top 10%
Top 10%
bronze