Format

Send to

Choose Destination
See comment in PubMed Commons below
J Recept Signal Transduct Res. 2010 Dec;30(6):430-43. doi: 10.3109/10799893.2010.518151. Epub 2010 Oct 14.

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

Author information

  • 1Laboratory of Transplantation Immunology and Nephrology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.

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 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.

CONCLUSIONS:

These data provide evidence that a burst of ZAP-70 activity initiates the signaling pathways for negative selection.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Taylor & Francis Icon for PubMed Central
    Loading ...
    Write to the Help Desk