The MHC class I ligand-generating system: roles of immunoproteasomes and the interferon-gamma-inducible proteasome activator PA28.

Production of antigenic peptides that serve as MHC class I ligands is essential for initiation of cell-mediated immunity. Accumulating evidence indicates that the proteasome, a large multisubunit protein deg radative machine in eukaryotes, functions as a processing enzyme responsible for the generation of MHC class I ligands. This processing system is elaborately regulated by various immunomodulatory cytokines. In particular, interferon-gamma induces the formation of immunoproteasomes and a recently identified proteasomal regulatory factor. PA28, which in concert contribute to efficient production of MHC class I ligands. Many of the MHC-encoded genes including LMP appear to have emerged by an ancient chromosomal duplication, suggesting that modifications and renewal of pre-existing non-immune genes were instrumental in the emergence of adaptive immunity.