Impaired immunoproteasome assembly and immune responses in PA28(-/-) mice

In vitro PA28 binds and activates proteasomes. It is shown here that mice w ith a disrupted PA28b gene Lack PA28a and PA28b polypeptides, demonstrating that PA28 functions as a hetero-oligomer in vivo. Processing of antigenic epitopes derived from exogenous or endogenous antigens is altered in PA28(- /-) mice. Cytotoxic T Lymphocyte responses are impaired, and assembly of im munoproteasomes is greatly inhibited in mice lacking PA28. These results sh ow that PA28 is necessary for immunoproteasome assembly and is required for efficient antigen processing, thus demonstrating the importance of PA28-me diated proteasome function in immune responses.