CD43 regulates the threshold for T cell activation by targeting Cbl functions

Gustavo Pedraza-Alva, Lilia B. Mérida, Roxana Del Rio, Nora A. Fierro, Mario E. Cruz-Muñoz, Norma Olivares, Erika Melchy, Vivian Igras, Georg A. Holländer, Steven J. Burakoff, Yvonne Rosenstein

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

T cell (TC) activation requires the coordinated signaling of the T cell receptor (TCR) and coreceptor molecules, allowing TCs to respond to lower degrees of TCR occupancy. Coreceptor molecules set the threshold for TC activation by controlling different regulatory signaling loops. The Cbl family members prevent undesired activation of T cells by regulating TCR signals. In this report, we show that TC prestimulation by the CD43 coreceptor molecule before TCR engagement inhibits TCR-dependent c-Cbl tyrosine phosphorylation, c-Cbl interaction with the adapter molecule Crk-L and promotes Cbl-b degradation in a PKCθ-dependent manner. Consequently, the prolonged tyrosine phosphorylation and delayed degradation of ZAP-70 and of the ζ chain lead to enhanced mitogen-activated protein kinase activation and robust TC response. These data indicates that CD43-mediated signals lower the threshold for TC activation by restricting the c-Cbl and Cbl-b inhibitory effects on TCR signaling. In addition to the strength and duration of intracellular signals, our data underscore temporality with which certain molecules are engaged as yet another mechanism to fine tune TC signal quality, and ultimately immune function.

Original languageEnglish
Pages (from-to)940-948
Number of pages9
JournalIUBMB Life
Volume63
Issue number10
DOIs
StatePublished - Oct 2011
Externally publishedYes

Keywords

  • CD43
  • Cbl
  • PKCθ
  • T cell activation

Fingerprint

Dive into the research topics of 'CD43 regulates the threshold for T cell activation by targeting Cbl functions'. Together they form a unique fingerprint.

Cite this