ArticleJournal of receptor and signal transduction research2010
A discrete affinity-driven elevation of ZAP-70 kinase activity initiates negative selection.
Article in Journal of receptor and signal transduction research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Tuning ITAM multiplicity on T cell receptors can control potency and selectivity to ligand density.Science signaling · 2018Article
- A novel Zap70 mutation with reduced protein stability demonstrates the rate-limiting threshold for Zap70 in T-cell receptor signalling.Immunology · 2014Article
- How the TCR balances sensitivity and specificity for the recognition of self and pathogens.Nature immunology · 2012Review
- Signaling in thymic selection.Current opinion in immunology · 2011Review
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
contextAlthough ZAP-70 is required for T-cell development, it's unclear how this kinase controls both positive and negative selection. OBJECTIVE AND
methodsUsing OT-I pre-selection thymocytes and a panel of peptide major histocompatibility complex (pMHC) ligands of defined affinity, the recruitment, phosphorylation and activity of ZAP-70 was determined at the interface with antigen-presenting cells (APCs).
resultspMHC ligands promoting negative selection induce a discrete elevation of ZAP-70 recruitment, phosphorylation and enzymatic activity in the thymocyte:APCs interface. DISCUSSION: The quantity of ZAP-70 kinase activity per cell is a key parameter controlling the fate of a developing thymocyte since partial inhibition of ZAP-70 kinase activity converted negative into positive selection. Surprisingly, the amount of ZAP-70 enzymatic activity observed during negative selection is not controlled by differential phosphorylation of the ZAP-70 protein but rather by the total amount of T-cell receptor and co-associated ZAP-70 recruited to the thymocyte:APC interface.
conclusionsThese data provide evidence that a burst of ZAP-70 activity initiates the signaling pathways for negative selection.
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