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TCR Down-Regulation Controls Virus-Specific CD8+ T Cell Responses

Title: TCR Down-Regulation Controls Virus-Specific CD8+ T Cell Responses
Authors: Bonefeld, Charlotte Menné; Haks, Mariëlle; Nielsen, Bodil; von Essen, Marina; Boding, Lasse; Hansen, Ann Kathrine; Larsen, Jeppe Madura; Ødum, Niels; Krimpenfort, Paul; Kruisbeek, Ada; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup; Geisler, Carsten
Source: The Journal of Immunology ; volume 181, issue 11, page 7786-7799 ; ISSN 1550-6606 0022-1767
Publisher Information: Oxford University Press (OUP)
Publication Year: 2008
Description: 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.
Document Type: article in journal/newspaper
Language: English
DOI: 10.4049/jimmunol.181.11.7786
Availability: https://doi.org/10.4049/jimmunol.181.11.7786; https://academic.oup.com/jimmunol/article-pdf/181/11/7786/62724180/8189.pdf
Rights: https://academic.oup.com/pages/standard-publication-reuse-rights
Accession Number: edsbas.F1943AC
Database: BASE