The role of the proteasome system and the proteasome activator PA28 complex in the cellular immune response

The generation of antigenic peptides bound and presented to the immune syst em by MHC class I molecules predominantly depends on the function of the pr oteasome system. Stimulation of cells with interferon gamma induces the inc orporation of three active site bearing beta-subunits into the 20S proteaso me and the formation of the PA28 proteasome modulator complex. PA28 alters the cleavage properties of the proteasome and enhances MHC class I antigen presentation. Thus, by cytokine induced change of the proteasome system cel ls may alter the proteolytic properties of the 20S proteasome and may rende r an organism more flexible in its peptide generation capacity.