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

被引:315
作者
Naramura, M
Jang, IK
Kole, H
Huang, F
Haines, D
Gu, H [1 ]
机构
[1] NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA
[2] NCI, Pathol Histotechnol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
关键词
D O I
10.1038/ni855
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1192 / 1199
页数:8
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