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

Immunol Rev. 1998 Jun;163:161-76. doi: 10.1111/j.1600-065x.1998.tb01195.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / immunology*
  • Chromosome Mapping
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / immunology*
  • Enzyme Activation
  • Gene Expression Regulation
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Interferon-gamma / immunology*
  • Ligands
  • Molecular Sequence Data
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / immunology*
  • Muscle Proteins*
  • Proteasome Endopeptidase Complex
  • Protein Conformation
  • Proteins / genetics
  • Proteins / immunology*
  • Ubiquitins / immunology


  • Histocompatibility Antigens Class I
  • Ligands
  • Multienzyme Complexes
  • Muscle Proteins
  • PSME1 protein, human
  • Proteins
  • Ubiquitins
  • Interferon-gamma
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex