Related Experiment Videos
c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation
Mayumi Naramura1, Ihn-Kyung Jang, Hemanta Kole
1Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Nature Immunology
|November 5, 2002
Summary
Cbl family proteins control T cell activation by clearing engaged T cell receptors (TCRs) from the cell surface. This process is crucial for terminating TCR signals and preventing T cell hyperresponsiveness.
Area of Science:
- Immunology
- Cell Biology
- Molecular Signaling
Background:
- The precise mechanisms by which Cbl family proteins regulate T cell responses remain incompletely understood.
- T cell activation is tightly controlled to prevent aberrant immune responses.
Purpose of the Study:
- To elucidate the role of Cbl family proteins, specifically c-Cbl and Cbl-b, in the regulation of T cell receptor (TCR) signaling and T cell activation.
Main Methods:
- Generation and analysis of c-Cbl and Cbl-b double knockout (dKO) T cells.
- Assessment of T cell hyperresponsiveness upon anti-CD3 stimulation.
- Evaluation of TCR signaling pathways, surface TCR down-modulation, and TCR internalization/trafficking.
Main Results:
- c-Cbl/Cbl-b dKO T cells exhibited hyperresponsiveness to anti-CD3 stimulation without enhanced canonical TCR signaling pathways.
- These dKO T cells failed to down-modulate surface TCR after ligand engagement, leading to sustained TCR signaling.
- Ligand-independent TCR internalization was normal, but trafficking of engaged TCR to lysosomes was reduced in dKO T cells.
Conclusions:
- Cbl family proteins act as negative regulators of T cell activation.
- They promote the clearance of engaged TCR from the cell surface, which is essential for terminating TCR signals.
- Dysregulation of this clearance mechanism contributes to T cell hyperresponsiveness.