Antigen presentation by MHC class I and its regulation by interferon gamma.
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.
The R. W. Johnson Pharmaceutical Research Institute, General Atomics Court, San Diego, CA 92121, USA. kfrueh@prius.jnj.com.
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D017951:Antigen Presentation / Q000187:drug effects*; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D046988:Proteasome Endopeptidase Complex
D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex