Journal
NATURE IMMUNOLOGY
Volume 3, Issue 12, Pages 1192-1199Publisher
NATURE AMERICA INC
DOI: 10.1038/ni855
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- NCI NIH HHS [N01-CO-56000] Funding Source: Medline
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How Cbl family proteins regulate T cell responses is unclear. We found that c-Cbl Cbl-b double knockout (dKO) T cells became hyperresponsive upon anti-CD3 stimulation, even though the major T cell antigen receptor (TCR) signaling pathways were not enhanced. The dKO T cells did not down-modulate surface TCR after ligand engagement, which resulted in sustained TCR signaling. However, these cells showed normal ligand-independent TCR internalization, and trafficking of internalized TCR to the lysosome compartment after ligand engagement was reduced. These findings show that Cbl family proteins negatively regulate T cell activation by promoting clearance of engaged TCR from the cell surface, a process that is apparently essential for the termination of TCR signals.
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