Immunoproteasomes are essential for survival and expansion of T cells in virus-infected mice

Authors

  • Jacqueline Moebius,

    1. Division of Immunology, Department of Biology, Constance University, Konstanz, Germany
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  • Maries van den Broek,

    1. Laboratory of Cancer Biology, Department of Oncology, University Hospital Zürich, Zürich, Switzerland
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  • Marcus Groettrup,

    Corresponding author
    1. Division of Immunology, Department of Biology, Constance University, Konstanz, Germany
    2. Biotechnology Institute Thurgau at the University of Constance, Kreuzlingen, Switzerland
    • Division of Immunology, University of Constance, Universitätsstrasse 10, D-78457 Konstanz, Germany Fax: +49-7531-883102
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  • Michael Basler

    1. Division of Immunology, Department of Biology, Constance University, Konstanz, Germany
    2. Biotechnology Institute Thurgau at the University of Constance, Kreuzlingen, Switzerland
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Abstract

Immunoproteasomes containing the IFN-inducible subunits β1i (LMP2), β2i (MECL-1) and β5i (LMP7) alter proteasomal cleavage preference and optimize the generation of peptide ligands of MHC class I molecules. Here, we report on an unexpected new function of immunoproteasome subunits for the survival and expansion of CD4+ and CD8+ T cells during viral infection of mice. The effect of immunoproteasome subunit deficiency on T-cell survival upon adoptive transfer was most prominent for the lack of LMP7 followed by MECL-1 and LMP2. The survival of T cells in uninfected mice or the homeostatic expansion after transfer into RAG-2−/− mice was not affected by the lack of the immunosubunits. Lymphocytic choriomeningitis virus (LCMV)-specific CD8+ T cells lacking LMP7 or MECL-1 started to divide after transfer into LCMV-infected mice but experienced a considerable cell loss within 2 days after transfer. We provide strong evidence that the loss of immunoproteasome-deficient T cells after transfer is not a consequence of graft rejection by the host, but instead is based on the requirement for immunoproteasomes for the survival of T cells in LCMV-infected mice. Therefore, the immunoproteasome may qualify as a potential new target for the suppression of undesired proinflammatory T-cell responses.

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