CD28 as a molecular amplifier extending TCR ligation and signaling capabilities

Frédérique Michel, Géraldine Attal-Bonnefoy, Giorgio Mangino, Setsuko Mise-Omata, Oreste Acuto

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Evidence has gathered that CD28 costimulation facilitates T cell activation by potentiating TCR intrinsic-signaling. However, the underlying molecular mechanism is largely unknown. Here we show that, by enhancing T cell/APC close contacts, CD28 facilitates TCR signal transduction. Moreover, the signal supplied by CD28 does not lead to increased Zap-70 and Lat phosphorylation, but amplifies PLCγ1 activation and Ca2+ response. We provide evidence that the PTK Itk controls the latter function. Our data suggest that CD28 binding to B7 contributes to setting the level of TCR-induced phosphorylated Lat for recruiting signaling complexes, whereas the CD28 signal boosts multiple pathways by facilitating PLCγ1 activation. These results should provide a conceptual framework for understanding quantitative and qualitative aspects of CD28-mediated costimulation.

Original languageEnglish
Pages (from-to)935-945
Number of pages11
JournalImmunity
Volume15
Issue number6
DOIs
Publication statusPublished - 2001 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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