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

  1. Author:
    Naramura, M.
    Jang, I. K.
    Kole, H.
    Huang, F.
    Haines, D.
    Gu, H.

  2. Author Address

    NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA NCI, Pathol Histotechnol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA Gu H NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA
    1. Year: 2002
  2. Journal: Nature Immunology
    1. 3
    2. 12
    3. Pages: 1192-1199
  4. Type of Article: Article
  1. Abstract:

    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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