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.
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.
- Dmitriy M Chudakov
- David A Price
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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.
- Armita Nourmohammad, University of Washington, United States
© 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.
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