Intracellular processing of viral and tumour antigens by proteasomes

Cytotoxic T cells are able to recognise whether a cell of our body is infec ted by a virus or whether it has acquired mutations leading to tumour forma tion. 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 in tact proteins but as peptide fragments which originate from their regular i ntracellular degradation. This fragmentation is accomplished by the proteas ome, 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 pepti de antigens. In this review we introduce the system of antigen processing b y the proteasome and sum up our latest results on the question how the inte rferon-gamma-mediated reorganisation of the proteasome occurs and what cons equences and benefits this has for the cytotoxic immune response against vi ruses and tumours.