Variability and robustness in T cell activation from regulated heterogeneity in protein levels Journal Article
| Authors: | Feinerman, O.; Veiga, J.; Dorfman, J. R.; Germain, R. N.; Altan-Bonnet, G. |
| Article Title: | Variability and robustness in T cell activation from regulated heterogeneity in protein levels |
| Abstract: | 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. |
| Keywords: | signal transduction; protein expression; cd8 antigen; cd8-positive t-lymphocytes; phenotype; cytology; animals; mice; cells, cultured; gene expression; protein; cell population; mice, inbred c57bl; mice, transgenic; gene expression regulation; lymphocyte activation; antigen; receptors, antigen, t-cell; eukaryota; mitogen activated protein kinase 3; ligands; computer simulation; eukaryotic cell; computer model; phenotypic variation; t lymphocyte activation; protein tyrosine phosphatase shp 1; feedback, biochemical; antigens, cd8; clone; heterogeneity; mitogen-activated protein kinase 3; stochasticity; biodiversity; models, immunological; protein tyrosine phosphatase, non-receptor type 6 |
| Journal Title: | Science |
| Volume: | 321 |
| Issue: | 5892 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2008-08-22 |
| Start Page: | 1081 |
| End Page: | 1084 |
| Language: | English |
| DOI: | 10.1126/science.1158013 |
| PUBMED: | 18719282 |
| PROVIDER: | scopus |
| PMCID: | PMC2673522 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 58" - "Export Date: 17 November 2011" - "CODEN: SCIEA" - "Source: Scopus" |
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Veiga
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