The role of CD4-Lck in T-cell receptor antagonism: evidence for negative signaling.

Journal Article

Small changes in the complex between a peptide and a molecule of the major histocompatibility complex generate ligands able to partially activate (partial agonist) or even inhibit (antagonist) T-cell functions. T-cell receptor engagement of antagonist complex results in a partial zeta chain phosphorylation without activation of the associated ZAP-70 kinase. Herein we show that, despite a strong inhibition of both inositol phospholipid hydrolysis and extracellular increasing antagonist concentrations increased the activity of the CD4-Lck kinase. Addition of anti-CD4 antibody to culture medium prevented inhibitory effects induced by antagonist ligand. We propose that CD4-Lck activation triggered by antagonist complexes may act in a dominant negative mode, thus overriding stimulatory signals coming from agonist ligand. These findings identify a new T-cell signaling profile that may explain the ability of some T-cell receptor variant ligands to inhibit specific biological activities or trigger alternative activation programs.

Full Text

Duke Authors

Cited Authors

  • Racioppi, L; Matarese, G; D'Oro, U; De Pascale, M; Masci, AM; Fontana, S; Zappacosta, S

Published Date

  • September 17, 1996

Published In

Volume / Issue

  • 93 / 19

Start / End Page

  • 10360 - 10365

PubMed ID

  • 8816805

International Standard Serial Number (ISSN)

  • 0027-8424

Language

  • eng

Conference Location

  • United States