The immunoproteasome in antigen processing and other immunological functions

Treatment of cells with interferon-gamma leads to the replacement of the constitutive catalytic proteasome subunits 131, 132, and 135 by the inducible subunits LMP2 (beta 1i), MECL-1 (beta 2i), and LMP7 (beta 5i), 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 beta 5i 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.