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 ORCID: https://orcid.org/0000-0001-9416-2737 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:	19 Oct 2022 10:41
URI:	https://orca.cardiff.ac.uk/id/eprint/25207

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