A role for the proteasome regulator PA28α in antigen presentation

CYTOTOXIC T cells recognize viral proteins as peptide fragments which are produced in the cytosol and transported on major histocompatibility complex (MHC) class I proteins to the cell surface¹. Viral peptides that meet the stringent binding characteristics of class I proteins are generated by the 20S proteasome^2,3. The interferon (IFN)-γ-inducible activator of the 20S proteasome, PA28 (refs 4-6), strongly influences the proteasomal cleavage pattern in vitro⁷. This led us to investigate whether changes in cellular levels of PA28 affect the efficiency of viral antigen processing. A mouse fibroblast line expressing the murine cytomegalovirus pp89 protein was transfected with either the human or murine gene encoding the PA28a subunit, which is sufficient to activate the peptide-hydrolysing activity of the 20S proteasome in vitro. Here we report that enhanced expression of PA28α at a level similar to that obtained after IFN-γ induction resulted in a marked enhancement of recognition by pp89-specific cytotoxic T cells; the presentation of influenza nucleoprotein was also significantly improved. These results demonstrate a fundamental in vivo function for PA28α in antigen processing.