Proteasomes in immune cells: more than peptide producers?
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.
Groettrup
Marcus
M
Division of Immunology, Department of Biology, University of Constance, Konstanz, Germany. Marcus.Groettrup@uni-konstanz.de
Kirk
Christopher J
CJ
Basler
Michael
M
D000818:Animals; D017951:Antigen Presentation; D001327:Autoimmune Diseases / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046988:Proteasome Endopeptidase Complex / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology* / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell; D046988:Proteasome Endopeptidase Complex