Coordinated dual cleavages induced by the proteasome regulator PA28 lead to dominant MHC ligands

The gamma-interferon inducible PA28 protein complex, or 11S regulator, which is composed of two homologous subunit forming a hexa- or heptameric ring structure, is known to associate with the 20S proteasome particle. The kinetics of product generation by 20S proteasomes with and without PA28 is studied. Results indicate that the PA28 regulator significantly alters the cleavage mechanism of the proteasome and optimizes the generation of dominant T cell epitopes.