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| Status |
Public on Sep 06, 2023 |
| Title |
Antigen perception in T cells by long-term Erk and NFAT signaling dynamics [RNAseq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Immune system threat detection hinges on T cells’ ability to perceive varying peptide major-histocompatibility complex (pMHC) antigens. As the Erk and NFAT pathways link T cell receptor engagement to gene regulation, their signaling dynamics may convey information about pMHC inputs. To test this idea, we developed a dual reporter mouse strain and a quantitative imaging assay that, together, enable simultaneous monitoring of Erk and NFAT dynamics in live T cells over day-long timescales as they respond to varying pMHC inputs. Both pathways initially activate uniformly across various pMHC inputs, but diverge only over longer (9+ hrs) timescales, enabling independent encoding of pMHC affinity and dose. These late signaling dynamics are decoded via multiple temporal and combinatorial mechanisms to generate pMHC-specific transcriptional responses. Our findings underscore the importance of long timescale signaling dynamics in antigen perception, and establish a framework for understanding T cell responses under diverse contexts.
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| Overall design |
CD8+ T cells were isolated from splenocytes and stimulated with high affinity antigen stimulation (2 pmol M9C). After 9 hours, cells were treated with either 1 uM Trametinib (MEK inhibitor), 1 uM Cyclosporin A (Calcineurin inhibitor), both, or DMSO (0.1%), and cultured for an additional 21 hours.
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| Contributor(s) |
Wither MJ, White WL, Pendyala S, Leanza PJ, Fowler D, Kueh HY |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Sep 06, 2023 |
| Last update date |
Sep 07, 2023 |
| Contact name |
Hao Yuan Kueh |
| E-mail(s) |
kueh@uw.edu
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| Organization name |
University of Washington
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| Department |
Bioengineering
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| Lab |
Kueh Lab
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| Street address |
3720 15th Ave NE
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98195 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| GSM7763376 |
mouse CD8, MEKi+CsA, 30hr, rep 1 |
| GSM7763377 |
mouse CD8, DMSO, 30hr, rep 2 |
| GSM7763378 |
mouse CD8, MEKi, 30hr, rep 2 |
| GSM7763379 |
mouse CD8, CsA, 30hr, rep 2 |
| GSM7763380 |
mouse CD8, MEKi+CsA, 30hr, rep 2 |
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| This SubSeries is part of SuperSeries: |
| GSE242495 |
Antigen perception in T cells by long-term Erk and NFAT signaling dynamics |
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| Relations |
| BioProject |
PRJNA1013393 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE242418_RAW.tar |
363.1 Mb |
(http)(custom) |
TAR (of H5, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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