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

Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 10/2010; 107(45):19414-9. DOI: 10.1073/pnas.1010586107
Source: PubMed

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.

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Available from: Miles P Davenport, Aug 01, 2014
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    • "Public sequences have a very high level of convergent recombination Previous studies reported that public TCRs manifest a higher level of convergent recombination (Venturi et al. 2006, 2011; Quigley et al. 2010; Li et al. 2012). Our analysis of a large number of individuals revealed a continuous trend; increased sharing was associated with a gradual increase in the mean degree of convergent recombination (Fig. 2A); private CDR3 aa sequences were encoded on average by one nt sequence, the public sequences were encoded by 34.5 nt sequences on average. "
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    • "acid multiple sequence alignment . We observed that the center of the TRBD is more conserved than the flanking regions . This could be explained by nucleotide nibbling ( Murphy et al . 2007 ) , though the bias for calling TRBD gene segments cannot be fully ruled out . Regardless , this is consistent with previous reports ( Freeman et al . , 2009 ; Quigley et al . , 2010 ) ."
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    Protein & Cell 05/2014; 5(8). DOI:10.1007/s13238-014-0060-1 · 2.85 Impact Factor
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    • "quences make up a " public " repertoire common to many individuals, formed through convergent evolution or a common source. However, it is also possible that these common sequences are just statistically more frequent, and are likely to be randomly recombined in two individuals independently, as previously discussed by Venturi et al. [6] [7] [21]. In other words, public sequences could just be chance events. "
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