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 Citations (Scopus)

Abstract

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
Volume15
Issue number8
DOIs
StatePublished - Aug 1 2003

Fingerprint

Helper-Inducer T-Lymphocytes
T-Cell Antigen Receptor
Cyclic AMP
Calcium
Antigens
Peptides
Phosphoric Diester Hydrolases
Second Messenger Systems
Adenylyl Cyclases
T-Lymphocytes

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

T cell receptor-independent CD4 signalling : CD4-MHC class II interactions regulate intracellular calcium and cyclic AMP. / Zhou, Wenhong; König, Rolf.

In: Cellular Signalling, Vol. 15, No. 8, 01.08.2003, p. 751-762.

Research output: Contribution to journalArticle

@article{076fdd9a28c54ee48e2786d280d4540e,
title = "T cell receptor-independent CD4 signalling: CD4-MHC class II interactions regulate intracellular calcium and cyclic AMP",
abstract = "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.",
keywords = "Activation, Adenylyl cyclas, Phosphodiesterase, Signal transduction, T lymphocytes",
author = "Wenhong Zhou and Rolf K{\"o}nig",
year = "2003",
month = "8",
day = "1",
doi = "10.1016/S0898-6568(03)00037-8",
language = "English (US)",
volume = "15",
pages = "751--762",
journal = "Cellular Signalling",
issn = "0898-6568",
publisher = "Elsevier Inc.",
number = "8",

}

TY - JOUR

T1 - T cell receptor-independent CD4 signalling

T2 - CD4-MHC class II interactions regulate intracellular calcium and cyclic AMP

AU - Zhou, Wenhong

AU - König, Rolf

PY - 2003/8/1

Y1 - 2003/8/1

N2 - 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.

AB - 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.

KW - Activation

KW - Adenylyl cyclas

KW - Phosphodiesterase

KW - Signal transduction

KW - T lymphocytes

UR - http://www.scopus.com/inward/record.url?scp=0038359096&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038359096&partnerID=8YFLogxK

U2 - 10.1016/S0898-6568(03)00037-8

DO - 10.1016/S0898-6568(03)00037-8

M3 - Article

C2 - 12781868

AN - SCOPUS:0038359096

VL - 15

SP - 751

EP - 762

JO - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

IS - 8

ER -