Variability and Robustness in T Cell Activation from Regulated Heterogeneity in Protein Levels
By Ofer Feinerman, Joël Veiga, J. Dorfman, Ronald N. Germain, G. Altan-Bonnet. Science, 2008
363 citations recorded by the source corpus.
In T cells, the stochasticity of protein expression could contribute to the useful diversification of biological functions within a clonal population or interfere with accurate antigen discrimination. Combining computer modeling and single-cell measurements, we examined how endogenous variation in the expression levels of signaling proteins might affect antigen responsiveness during T cell activation. We found that the CD8 co-receptor fine-tunes activation thresholds, whereas the soluble hematopoietic phosphatase 1 (SHP-1) digitally regulates cell responsiveness. Stochastic variation in the expression of these proteins generates substantial diversity of activation within a clonal population of T cells, but co-regulation of CD8 and SHP-1 levels ultimately limits this very diversity. These findings reveal how eukaryotic cells can draw on regulated variation in gene expression to achieve phenotypic variability in a controlled manner.
Subfields: Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/5f5c25888fc98243344e0d268ff15f46674a5daf
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In Immunology
In Molecular Biology
- Peter K. Sorger
- Gustavo A. Stolovitzky
- Robert J. Prill
- G. Altan-Bonnet
- J. Sáez-Rodríguez
- Neil D. Clarke
- Daniel Marbach
- Peter Buhlmann
Citations in the corpus
- PD-1 signaling in primary T cells (2009, background): “SHP-1 was recently shown to be a digital regulator of T-cell activation (79).”
- Towards a Rigorous Assessment of Systems Biology Models: The DREAM3 Challenges (2010, background): “The biological motivation of the T cell experiment is discussed in [13].”