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

Michal Mark*, Shlomit Reich-Zeliger, Erez Greenstein, Dan Reshef, Asaf Madi, Benny Chain*, Nir Friedman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.
Original languageEnglish
Article number939394
Number of pages19
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 29 Jul 2022

Funding

BC was supported by a Weston Visiting Professorship from the Weizmann Institute of Science, and by a grant from the Rosetrees Foundation, UK. NF was supported by the Applebaum Family Foundation.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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