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

Mayumi Naramura, Ihn Kyung Jang, Hemanta Kole, Fang Huang, Diana Haines, Hua Gu

Research output: Contribution to journalArticle

275 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1192-1199
Number of pages8
JournalNature Immunology
Volume3
Issue number12
DOIs
StatePublished - Dec 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Naramura, M., Jang, I. K., Kole, H., Huang, F., Haines, D., & Gu, H. (2002). C-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation. Nature Immunology, 3(12), 1192-1199. https://doi.org/10.1038/ni855