Functionally specialized human CD4+ T cell subsets express physicochemically distinct TCRs
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Federation
- Cardiff University School of Medicine, United Kingdom
- Central European Institute of Technology, Czech Republic
- Lomonosov Moscow State University, Russian Federation
Abstract
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 ab 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.
Data availability
All extracted repertoires and metadata are deposited in Figshare: https://figshare.com/s/2145b1b16c6854445af7 and https://figshare.com/s/84ec5f412356afb0536d.
-
Human effector/memory CD4 T cell subsets: deep TCR profiling.NCBI Gene Expression Omnibus, GSE158848.
Article and author information
Author details
Elena K Matveishina
Dmitriy M Chudakov
Funding
Ministry of Science and Higher Eductaion of Russian Federation (075-15-2019-1789)
- Dmitriy M Chudakov
Wellcome Trust (100326/Z/12/Z)
- David A Price
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Ethical approval was granted by the institutional review committees at Cardiff University School of Medicine (reference number 16/55) and the Pirogov Russian National Research Medical University (protocol number 2017/52) and all donors provided informed consent for their participation in the study.
Copyright
© 2020, Kasatskaya et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,946
- views
-
- 395
- downloads
-
- 21
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Citations by DOI
-
- 21
- citations for umbrella DOI https://doi.org/10.7554/eLife.57063
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Functionally specialized human CD4+ T cell subsets express physicochemically distinct TCRs
eLife 9:e57063.
https://doi.org/10.7554/eLife.57063
