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 language | English (US) |
|---|---|
| Pages (from-to) | 751-762 |
| Number of pages | 12 |
| Journal | Cellular Signalling |
| Volume | 15 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2003 |
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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 journal › Article
}
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 -