A discrete affinity-driven elevation of ZAP-70 kinase activity initiates negative selection.

ABSTRACT:

Context

Although ZAP-70 is required for T-cell development, it's unclear how this kinase controls both positive and negative selection.

Objective and methods

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).

Results

pMHC 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

SUBMITTER: Mallaun M 

PROVIDER: S-EPMC3056388 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature