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

The CD3 gamma di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3 gamma 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 CD3 gamma di-leucine-based motif. The CD3 gamma 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 CD3 gamma-mediated TCR down-regulation in virus-specific CD8(+) T cell responses. The Journal of Immunology, 2008, 181: 7786-7799.