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Charlotte Menné Bonefeld, Mariëlle Haks, Bodil Nielsen, Marina von Essen, Lasse Boding, Ann Kathrine Hansen, Jeppe Madura Larsen, Niels Ødum, Paul Krimpenfort, Ada Kruisbeek, Jan Pravsgaard Christensen, Allan Randrup Thomsen, Carsten Geisler, TCR Down-Regulation Controls Virus-Specific CD8+ T Cell Responses, The Journal of Immunology, Volume 181, Issue 11, December 2008, Pages 7786–7799, https://doi.org/10.4049/jimmunol.181.11.7786
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Abstract
The CD3γ di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3γ 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 CD3γ di-leucine-based motif. The CD3γ 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 CD3γ-mediated TCR down-regulation in virus-specific CD8+ T cell responses.