Intracellular processing of viral and tumor antigens by proteasomes

Abstract

Cytotoxic T cells are able to recognise whether a cell of our body is infected by a virus or whether it has acquired mutations leading to tumour formation. The cells show on their surface what kind of proteins are synthesised intracellularly and whether non-self proteins encoded by a virus or tumour antigens are among them. The proteins are presented not as functionally intact proteins but as peptide fragments which originate from their regular intracellular degradation. This fragmentation is accomplished by the proteasome, a large proteinase complex in the cytoplasm and nucleus of all cells. Upon stimulation with the antiviral cytokine interferon-gamma, subunits of the proteasome are exchanged, thus leading to optimised production of peptide antigens. In this review we introduce the system of antigen processing by the proteasome and sum up our latest results on the question how the interferon-gamma-mediated reorganisation of the proteasome occurs and what consequences and benefits this has for the cytotoxic immune response against viruses and tumours.