Variability and robustness in T cell activation from regulated heterogeneity in protein levels.


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.

DOI: 10.1126/science.1158013

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@article{Feinerman2008VariabilityAR, title={Variability and robustness in T cell activation from regulated heterogeneity in protein levels.}, author={Ofer Feinerman and J Pedro Veiga and Jeffrey R Dorfman and Ronald N. Germain and Gr{\'e}goire Altan-Bonnet}, journal={Science}, year={2008}, volume={321 5892}, pages={1081-4} }