TCR down-regulation controls virus-specific CD8+ T cell responses

J Immunol. 2008 Dec 1;181(11):7786-99. doi: 10.4049/jimmunol.181.11.7786.


The CD3gamma di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3gamma di-leucine-based motif in physiological T cell responses. In this study, we show that the expansion in numbers of virus-specific CD8(+) T cells is impaired in mice with a mutated CD3gamma di-leucine-based motif. The CD3gamma mutation did not impair early TCR signaling, nor did it compromise recruitment or proliferation of virus-specific T cells, but it increased the apoptosis rate of the activated T cells by increasing down-regulation of the antiapoptotic molecule Bcl-2. This resulted in a 2-fold reduction in the clonal expansion of virus-specific CD8(+) T cells during the acute phase of vesicular stomatitis virus and lymphocytic choriomeningitis virus infections. These results identify an important role of CD3gamma-mediated TCR down-regulation in virus-specific CD8(+) T cell responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / genetics
  • Amino Acid Motifs / immunology
  • Animals
  • Arenaviridae Infections / genetics
  • Arenaviridae Infections / immunology*
  • CD3 Complex / genetics
  • CD3 Complex / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Down-Regulation / immunology*
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Mice, Transgenic
  • Mutation / immunology
  • Peptides / immunology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Rhabdoviridae Infections / genetics
  • Rhabdoviridae Infections / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Vesiculovirus / immunology*
  • Viral Proteins / immunology


  • CD3 Complex
  • CD3 antigen, gamma chain
  • Peptides
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, T-Cell
  • Viral Proteins