|
|
|
|
|
|
|
||
J. Exp. Med.,
Volume 187, Number 10, May 18, 1998 1699-1709
By
From the * Transplantation and Immunobiology Group, The T cell receptor (TCR) is a versatile receptor able to generate different signals that result in
distinct T cell responses. The pattern of early signals is determined by the TCR binding kinetics that control the ability of the ligand to coengage TCR and coreceptor. Coengagement of
TCR and CD4 results in an agonist signaling pattern with complete tyrosine phosphorylation
of TCR subunits, and recruitment and activation of ZAP-70. In contrast, TCR engagement
without CD4 coengagement causes a partial agonist type of signaling, characterized by distinct
phosphorylation of TCR subunits and recruitment but no activation of ZAP-70. The pathways
triggered by partial agonist signaling are unknown. Here, we show that agonists cause association of active lck and active ZAP-70 with p120-GTPase-activating protein (p120-GAP). These
associations follow engagement of CD4 or CD3, respectively. In contrast, partial agonists do
not activate lck or ZAP-70, but induce association of p120-GAP with inactive ZAP-70. Despite these differences, both agonist and partial agonist signals activate the mitogen-activated protein kinase (MAPK) pathway. However, MAPK activation by partial agonists is transient,
supporting a kinetic, CD4-dependent model for the mechanism of action of variant TCR
ligands. Transient MAPK activation may explain some of the responses to TCR partial agonists
and antagonists.
Departments of Microbiology and Immunology and Medicine,
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
