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| Status |
Public on Jan 16, 2021 |
| Title |
T cell self-reactivity during thymic development dictates the timing of positive selection |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Functional tuning of mature 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 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 suggest that modulation of membrane ion channel function may play a role in regulating TCR tuning throughout development.
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| Overall design |
RNA-seq was performed on FACS sorted thymocytes from three OT-1 Rag2KO, three F5 Rag1KO, and three TG6 H2b/d mice (biological replicates). Thymocytes were sorted into 3 populations representing 3 distinct stages of CD8 T cell positive selection prior to sequencing: CD4+CD8+CXCR4+CCR7- (C, early positive selection), CD4+CD8+CXCR4-CCR7+ (B, late positive selection) [TG6 only has two biological replicates for this population], and CD4-CD8+CXCR4-CCR7+ (A, Mature CD8SP). This resulted in 26 samples in total.
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| Contributor(s) |
Lutes LK, Steier Z, McIntyre LL, Pandey S, Kaminski J, Hoover AR, Ariotti S, Streets A, Yosef N, Robey EA |
| Citation(s) |
33884954 |
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| Submission date |
Jan 15, 2021 |
| Last update date |
Apr 28, 2021 |
| Contact name |
Zoë Steier |
| E-mail(s) |
zsteier@berkeley.edu
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| Organization name |
UC Berkeley
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| Street address |
378 Stanley Hall
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| City |
Berkeley |
| State/province |
CA |
| ZIP/Postal code |
94720 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (26)
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| Relations |
| BioProject |
PRJNA692420 |
| SRA |
SRP301926 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE164896_normalized_counts.csv.gz |
3.9 Mb |
(ftp)(http) |
CSV |
| GSE164896_txi_rsem_transcript_counts.rds.gz |
7.2 Mb |
(ftp)(http) |
RDS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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