T cell self-reactivity during thymic development dictates the timing of positive selection
- University of California, Berkeley, United States
- Boston Children's Hospital, United States
- University of Lisbon, Portugal
Abstract
Functional tuning of T cells based on their degree of self-reactivity is established during positive selection in the thymus, although how positive selection differs for thymocytes with relatively low versus high self-reactivity is unclear. In addition, preselection thymocytes are highly sensitive to low-affinity ligands, but the mechanism underlying their enhanced TCR sensitivity is not fully understood. Here we show that murine thymocytes with low self-reactivity experience briefer TCR signals and complete positive selection more slowly than those with high self-reactivity. Additionally, we provide evidence that cells with low self-reactivity retain a preselection gene expression signature as they mature, including genes previously implicated in modulating TCR sensitivity and a novel group of ion channel genes. Our results imply that thymocytes with low self-reactivity down-regulate TCR sensitivity more slowly during positive selection, and associate membrane ion channel expression with thymocyte self-reactivity and progress through positive selection.
Data availability
RNA-seq data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE164896.
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T cell self-reactivity during thymic development dictates the timing of positive selectionNCBI Gene Expression Omnibus, GSE164896.
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ImmGen Microarray Phase 1NCBI Gene Expression Omnibus, GSE15907.
Article and author information
Author details
Funding
National Institutes of Health (RO1AI064227)
- Ellen A Robey
National Institutes of Health (T32AI100829)
- Laura L McIntyre
- Ashley R Hoover
Human Frontiers Fellowship
- Silvia Ariotti
National Science Foundation (GRFP)
- Zoë Steier
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All mice were bred and maintained under pathogen-free conditions in an American Association of Laboratory Animal Care-approved facility at the University of California, Berkeley. The University of California, Berkeley Animal Use and Care Committee approved all procedures (Animal Care and Use Protocol #AUP-2016-07-9006).
Copyright
© 2021, Lutes 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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T cell self-reactivity during thymic development dictates the timing of positive selection
eLife 10:e65435.
https://doi.org/10.7554/eLife.65435
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