The immunoproteasome in antigen processing and other immunological functions

Treatment of cells with interferon-γ leads to the replacement of the constitutive catalytic proteasome subunits β1, β2, and β5 by the inducible subunits LMP2 (β1i), MECL-1 (β2i), and LMP7 (β5i), respectively, building the so-called immunoproteasome. The incorporation of these subunits is required for the production of numerous MHC class-I restricted T cell epitopes. Recently, new evidence for an involvement of the immunoproteasome in other facets of the immune response emerged. Investigations of autoimmune diseases in animal models and a genetic predisposition of β5i in human autoimmune disorders suggest a crucial function of the immunoproteasome in proinflammatory diseases. The recent elucidation of the high-resolution structure of the immunoproteasome will facilitate the design of immunoproteasome selective inhibitors for pharmacological intervention.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (288 K)Download as PowerPoint slideHighlights► Lessons from the high resolution structure of the immunoproteasome about its function. ► The antigen processing phenotype of mice devoid of all immunoproteasome subunits. ► The function of the immunoproteasome in directing T helper cell differentiation. ► The potential of LMP7 inhibitors for the treatment of autoimmune diseases. ► The symptoms of human diseases caused by mutations in the PSMB8 gene encoding LMP7.