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Proteasomes in immune cells: more than peptide producers?

Nature Reviews Immunology volume 10, pages 73–78 (2010)Cite this article

Abstract

When cells are stimulated with pro-inflammatory cytokines, most of their constitutively expressed proteasomes are replaced with immunoproteasomes, which increase the production of peptides for presentation on MHC class I molecules. In addition, cortical thymic epithelial cells selectively express a type of proteasome known as the thymoproteasome that is required for the positive selection of thymocytes. Here, we discuss how these specialized types of proteasome shape the T cell receptor repertoire of cytotoxic T lymphocytes and propose that immunoproteasomes have functions, in addition to antigen processing, that influence cytokine production and T cell differentiation, survival and function. We also discuss how inhibitors of immunoproteasomes can suppress undesired T cell responses in autoimmune diseases.

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Figure 1: Antigen processing in the MHC class I-restricted pathway.
Figure 2: Subunit composition of the active sites of the constitutive proteasome, immunoproteasome and thymoproteasome.
Figure 3: Proteasomes in positive and negative selection in the thymus.

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Acknowledgements

We thank J. Moebius, K. W. Kalim, E. Suzuki and T. Muchamuel for the communication of data before they were accepted for publication. This work was supported by grants from the German Research Foundation (DFG) — GR1517/4-2 and GR1517/5-1 — and the Graduate School Chemical Biology at the University of Constance, Germany.

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  1. Marcus Groettrup and Michael Basler are at the Division of Immunology, Department of Biology, University of Constance, D-78,457 Konstanz, Germany, and at the Biotechnology Institute Thurgau (BITg) at the University of Constance, CH-8,280 Kreuzlingen, Switzerland.,

    Marcus Groettrup & Michael Basler

  2. Christopher J. Kirk is at Onyx Pharmaceuticals, Emeryville, California 94608, USA.,

    Christopher J. Kirk

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Correspondence to Marcus Groettrup.

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Groettrup, M., Kirk, C. & Basler, M. Proteasomes in immune cells: more than peptide producers?. Nat Rev Immunol 10, 73–78 (2010). https://doi.org/10.1038/nri2687

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