Peptide generation by the UPS (ubiquitin–proteasome system) is rate-limiting in MHC class I-restricted antigen presentation in response to virus-induced IFNs (interferons). In this process, the role of IFN-induced rapid remodelling of the UPS is less defined. IFN-mediated de novo formation of different proteasome compositions as i20S (immunoproteasomes) or m20S (mixed-type proteasomes) essentially supports the rapid adjustment of the mammalian immune system to pathogens. This adjustment is of particular importance for the immune response to rapidly replicating viruses. In agreement, i20S formation has been shown to be an accelerated and transient response. Moreover, i20S and/or PA28 (proteasome activator 28) are essentially required for the generation of certain viral epitopes. In the present paper, we discuss how IFNs consecutively regulate the UPS at different levels, thereby improving the immune responsiveness of target cells.

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