A ROLE FOR THE PROTEASOME REGULATOR PA28-ALPHA IN ANTIGEN PRESENTATION

CYTOTOXIC T cells recognize viral proteins as peptide fragments which are produced in the cytosol and transported on major histocompatibilit y complex (MHC) class I proteins to the cell surface(1). Viral peptide s that meet the stringent binding characteristics of class I proteins are generated by the 20S proteasome(2,3), The interferon (IFN)-gamma-i nducible activator of the 20S proteasome, PA28 (refs 4-6), strongly in fluences the proteasomal cleavage pattern in vitro(7), This led us to investigate whether changes in cellular levels of PA28 affect the effi ciency of viral antigen processing, A mouse fibroblast line expressing the murine cytomegalovirus pp89 protein was transfected with either t he human or murine gene encoding the PA28 alpha subunit, which is suff icient to activate the peptide-hydrolysing activity of the 20S proteas ome in vitro. Here we report that enhanced expression of PA28 alpha at a level similar to that obtained after IFN-gamma induction resulted i n a marked enhancement of recognition by pp89-specific cytotoxic T cel ls; the presentation of influenza nucleoprotein was also significantly improved, These results demonstrate a fundamental in vivo function fo r PA28 alpha in antigen processing.