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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, RESULTS. Meshes: Animals, Antigen-Presenting Cells, Ligands, Lymphocyte Activation, Major Histocompatibility Complex, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, ZAP-70 Protein-Tyrosine Kinase.
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Does a discrete affinity-driven elevation of ZAP-70 kinase activity initiate negative selection? Context: Although ZAP-70 is required for T-cell development, it's unclear how this kinase controls both positive and negative selection. Using 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). pMHC ligands promoting negative selection induce a discrete elevation of ZAP-70 recruitment, phosphorylation and enzymatic activity in the thymocyte:APCs interface.
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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. Final Decision: yes