c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation

M Naramura, IK Jang, H Kole, F Huang, D Haines… - Nature …, 2002 - nature.com
M Naramura, IK Jang, H Kole, F Huang, D Haines, H Gu
Nature immunology, 2002nature.com
How Cbl family proteins regulate T cell responses is unclear. We found that c-Cbl Cbl-b
double knock-out (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 …
Abstract
How Cbl family proteins regulate T cell responses is unclear. We found that c-Cbl Cbl-b double knock-out (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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