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

Charlotte Menné Bonefeld, Mariëlle Haks, Bodil Nielsen, Marina von Essen, Lasse Boding, Ann Kathrine Hansen, Jeppe Madura Larsen, Niels Odum, Paul Krimpenfort, Ada Kruisbeek, Jan Pravsgaard Christensen, Allan Randrup Thomsen, Carsten Geisler

    Publikation: Bidrag til tidsskriftTidsskriftsartikelForskningpeer review

    Abstract

    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.

    OriginalsprogEngelsk
    TidsskriftJournal of Immunology
    Vol/bind181
    Udgave nummer11
    Sider (fra-til)7786-99
    Antal sider14
    ISSN0022-1767
    DOI
    StatusUdgivet - 1 dec. 2008

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