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Two distinct pathways exist for down-regulation of the TCR
J P Lauritsen1, M D Christensen, J Dietrich
1Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute, Denmark.
Journal of Immunology (Baltimore, Md. : 1950)
|July 1, 1998
Summary
T-cell receptor (TCR) down-regulation occurs via two separate pathways: ligand engagement and protein kinase C (PKC) activation. These distinct mechanisms involve different molecular players, impacting T cell responses.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Signaling
Background:
- T-cell receptor (TCR) down-regulation is crucial for modulating T cell responses during development and in mature T cells.
- TCR down-regulation can be triggered by specific ligand engagement or protein kinase C (PKC) activation.
Purpose of the Study:
- To elucidate the distinct molecular mechanisms underlying ligand- and PKC-induced TCR down-regulation.
- To investigate the roles of specific kinases and internalization motifs in these processes.
Main Methods:
- Investigated the dependence of TCR down-regulation on protein tyrosine kinases (p56(lck), p59(fyn)) and the CD3gamma leucine-based (L-based) internalization motif.
- Differentiated between ligand-induced and PKC-induced TCR down-regulation pathways.
Main Results:
- Ligand-induced TCR down-regulation requires p56(lck) and p59(fyn) but not PKC or the CD3gamma L-based motif.
- PKC-induced TCR down-regulation depends on the CD3gamma L-based motif but is independent of p56(lck) and p59(fyn).
- TCR expression levels can be regulated independently of TCR ligation through the CD3gamma L-based motif, influenced by the balance of PKC and phosphatase activities.
Conclusions:
- Ligand and PKC activation utilize distinct, independent pathways to mediate TCR down-regulation.
- The CD3gamma L-based motif plays a critical role in PKC-induced down-regulation and basal TCR expression level control.
- TCR ligation-independent regulation of TCR expression may influence T cell activation thresholds upon encountering antigen-presenting cells (APCs).