The immunoproteasome and thymoproteasome: functions, evolution and human disease

Nat Immunol. 2018 Sep;19(9):923-931. doi: 10.1038/s41590-018-0186-z. Epub 2018 Aug 13.


The basic principle of adaptive immunity is to strictly discriminate between self and non-self, and a central challenge to overcome is the enormous variety of pathogens that might be encountered. In cell-mediated immunity, immunological discernment takes place at a molecular or cellular level. Central to both mechanisms of discernment is the generation of antigenic peptides associated with MHC class I molecules, which is achieved by a proteolytic complex called the proteasome. To adequately accomplish the discrimination between self and non-self that is essential for adaptive immunity and self-tolerance, two proteasome subtypes have evolved via gene duplication: the immunoproteasome and the thymoproteasome. In this Review, we describe various aspects of these immunity-dedicated proteasomes, from their discovery to recent findings.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity
  • Animals
  • Autoantigens / immunology
  • Autoimmune Diseases / immunology*
  • Evolution, Molecular*
  • Gene Duplication
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Peptides / immunology
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / immunology*
  • Proteolysis
  • Self Tolerance
  • Thymus Gland / immunology*


  • Autoantigens
  • Histocompatibility Antigens Class I
  • Peptides
  • Proteasome Endopeptidase Complex