Antigen presentation by MHC class I and its regulation by interferon gamma

Curr Opin Immunol. 1999 Feb;11(1):76-81. doi: 10.1016/s0952-7915(99)80014-4.


Antigen processing by MHC class I molecules begins with the generation of peptides by proteolytic breakdown of proteins. IFN-gamma upregulates gene expression of several proteasomal subunits as well as the proteasome regulator PA28; this implicated their role in antigen degradation. Crystallographic, mutational and biochemical studies contributed to our understanding of the basic principles of proteasomal protein degradation and the consequences of IFN-gamma induction for proteasome function. In addition, nonproteasomal mechanisms seem to be involved in antigen degradation. Leucine aminopeptidase, which is also upregulated by IFN-gamma, was shown to collaborate with the proteasome for epitope production and unknown proteases seem to compensate for the loss of proteasomal degradation in the presence of proteasome inhibitors. Thus, a rather complex picture emerges for the rules governing peptide production in the presence or absence of IFN-gamma.

Publication types

  • Review

MeSH terms

  • Antigen Presentation / drug effects*
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / drug effects
  • Cysteine Endopeptidases / immunology
  • Histocompatibility Antigens Class I / drug effects*
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Interferon-gamma / pharmacology*
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / drug effects
  • Multienzyme Complexes / immunology
  • Proteasome Endopeptidase Complex


  • Histocompatibility Antigens Class I
  • Multienzyme Complexes
  • Interferon-gamma
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex