Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2010-11, Vol.107 (45), p.19414-19419

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2010

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• 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.