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A hierarchy of selection pressures determines the organization of the T cell receptor repertoire

Mark, Michal; Reich-Zeliger, Shlomit; Greenstein, Erez; Reshef, Dan; Madi, Asaf; Chain, Benny; Friedman, Nir; (2022) A hierarchy of selection pressures determines the organization of the T cell receptor repertoire. Frontiers in Immunology , 13 , Article 939394. 10.3389/fimmu.2022.939394. Green open access

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Abstract

We systematically examine the receptor repertoire in T cell subsets in young, adult, and LCMV-infected mice. Somatic recombination generates diversity, resulting in the limited overlap between nucleotide sequences of different repertoires even within the same individual. However, statistical features of the repertoire, quantified by the V gene and CDR3 k-mer frequency distributions, are highly conserved. A hierarchy of immunological processes drives the evolution of this structure. Intra-thymic divergence of CD4+ and CD8+ lineages imposes subtle but dominant differences observed across repertoires of all subpopulations in both young and adult mice. Differentiation from naive through memory to effector phenotype imposes an additional gradient of repertoire diversification, which is further influenced by age in a complex and lineage-dependent manner. The distinct repertoire of CD4+ regulatory T cells is more similar to naive cells in young mice and to effectors in adults. Finally, we describe divergent (naive and memory) and convergent (CD8+ effector) evolution of the repertoire following acute infection with LCMV. This study presents a quantitative framework that captures the structure of the repertoire in terms of its fundamental statistical properties and describes how this structure evolves as individual T cells differentiate, migrate and mature in response to antigen exposure.

Type: Article
Title: A hierarchy of selection pressures determines the organization of the T cell receptor repertoire
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2022.939394
Publisher version: https://doi.org/10.3389/fimmu.2022.939394
Language: English
Additional information: © 2022 Mark, Reich-Zeliger, Greenstein, Reshef, Madi, Chain and Friedman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: TCR repertoire, CDR3AA motifs, LCMV, aging, epitope-specific repertoire
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10154690
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