Proteasomes in immune cells: more than peptide producers?

M Groettrup, CJ Kirk, M Basler - Nature Reviews Immunology, 2010 - nature.com
Nature Reviews Immunology, 2010nature.com
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 …
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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