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.
Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Japan. tanakak@rinshoken.or.jp
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D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002874:Chromosome Mapping; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008024:Ligands; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D009124:Muscle Proteins; D046988:Proteasome Endopeptidase Complex; D011487:Protein Conformation; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D014452:Ubiquitins / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D008024:Ligands; D009097:Multienzyme Complexes; D009124:Muscle Proteins; C085047:PSME1 protein, human; D011506:Proteins; D014452:Ubiquitins; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex