Journal
NATURE REVIEWS IMMUNOLOGY
Volume 10, Issue 1, Pages 72-77Publisher
NATURE PORTFOLIO
DOI: 10.1038/nri2687
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Funding
- German Research Foundation (DFG) [GR1517/4-2, GR1517/5-1]
- Graduate School Chemical Biology at the University of Constance, Germany
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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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