T cell receptor-independent CD4 signalling: CD4-MHC class II interactions regulate intracellular calcium and cyclic AMP

Wenhong Zhou, Rolf König

Research output: Contribution to journalArticle

11 Scopus citations


CD4 is a coreceptor on T helper (Th) cells that interacts with MHC class II molecules (MHCII). The mechanisms mediating the effects of CD4 on responses by T helper cells to stimulation of the antigen-specific T cell receptor (TCR) are still poorly understood. Here, we demonstrate T cell costimulation via CD4 signalling independent of T cell receptor-mediated signals. Incubation of T helper cells with peptide mimetics of the CD4-binding region on the MHC class II β2 domain caused intracellular calcium mobilization in the absence of antigen or other T cell receptor stimuli. Engagement of CD4 by peptide mimetics or wild-type MHC class II, but not by mutant MHC class II molecules incapable of engaging CD4, inhibited the T cell receptor-mediated increase in cyclic AMP (cAMP) concentrations in T helper cells. CD4-mediated signals activated cyclic AMP phosphodiesterases (PDEs) and inhibited adenylyl cyclase. Full activation and clonal expansion of antigen-stimulated T helper cells required the CD4-mediated regulation of cyclic AMP. Our results suggest a costimulatory mechanism of CD4 function that acts on the second messengers, calcium and cyclic AMP.

Original languageEnglish (US)
Pages (from-to)751-762
Number of pages12
JournalCellular Signalling
Issue number8
StatePublished - Aug 1 2003



  • Activation
  • Adenylyl cyclas
  • Phosphodiesterase
  • Signal transduction
  • T lymphocytes

ASJC Scopus subject areas

  • Cell Biology

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