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

• Published in: Current opinion in immunology 1999-02, Vol.11 (1), p.76-81
• Main Authors: Früh, Klaus, Yang, Young
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0952-7915; 1879-0372
• 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-γ 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-γ induction for proteasome function. In addition, nonproteasomal mechanisms seem to be involved in antigen degradation. Leucine aminopeptidase, which is also upregulated by IFN-γ, 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-γ.