Functionally specialized human CD4+ T-cell subsets express physicochemically distinct TCRs

doi:10.7554/eLife.57063

Functionally specialized human CD4+ T-cell subsets express physicochemically distinct TCRs

2020-12-08

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AI

Dmitriy B. Staroverov

Dmitriy M. Chudakov *

DOI：10.7554/eLife.57063

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Abstract

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The organizational integrity of the adaptive immune system is determined by functionally discrete subsets of CD4(+) T cells, but it has remained unclear to what extent lineage choice is influenced by clonotypically expressed T-cell receptors (TCRs). To address this issue, we used a high-throughput approach to profile the alpha beta TCR repertoires of human naive and effector/memory CD4(+) T-cell subsets, irrespective of antigen specificity. Highly conserved physicochemical and recombinatorial features were encoded on a subset-specific basis in the effector/memory compartment. Clonal tracking further identified forbidden and permitted transition pathways, mapping effector/memory subsets related by interconversion or ontogeny. Public sequences were largely confined to particular effector/memory subsets, including regulatory T cells (Tregs), which also displayed hardwired repertoire features in the naive compartment. Accordingly, these cumulative repertoire portraits establish a link between clonotype fate decisions in the complex world of CD4(+) T cells and the intrinsic properties of somatically rearranged TCRs.

Keywords:

FOLLICULAR HELPER

RECEPTOR REPERTOIRE

REGULATORY CELLS

THYMIC SELECTION

FOXP3 EXPRESSION

HUMAN TH1

IN-VITRO

DIFFERENTIATION

PLASTICITY

LINEAGE

Functionally specialized human CD4+ T-cell subsets express physicochemically distinct TCRs

Abstract

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