Proteasome function in antigen presentation: immunoproteasome complexes, Peptide production, and interactions with viral proteins.
Proteasomes are the major nonlysosomal protein degradation machinery in eukaryotic cells and they are largely responsible for the processing of antigens for presentation by the MHC class I pathway. This review concentrates on recent developments in the area of antigen processing. Specialized proteasomes called immunoproteasomes and an 11S regulator of proteasomes (PA28) are induced by interferon-gamma, but it is not entirely clear why changes in proteasome structure are beneficial for antigen presentation. Different proteasome complexes have distinct subcellular distributions and subtle differences in cleavage specificity. Thus it is likely that the efficiency of production of MHC class I binding peptides varies in different locations. Immunoproteasome subunits are enriched at the ER where TAP transports peptides for association with newly synthesized MHC class I molecules. There is recent evidence to suggest that antigen presentation from viral expression vectors, or from peptides that are either delivered by bacterial toxins or derived from signal peptides, require proteasome activity for generation of the correct C-terminus of the epitope. The correct N-terminus may be generated by recently identified ER associated aminopeptidases. A number of viral protein interactions with proteasome subunits have been reported and such interactions may interfere with host anti-viral defenses and also contribute to mechanisms of cell transformation.
Rivett
A Jennifer
AJ
Department of Biochemistry, University of Bristol, School of Medical Sciences, Bristol BS8 1TD, UK. j.rivett@bristol.ac.uk
Hearn
Arron R
AR
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D009097:Multienzyme Complexes / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism
D001427:Bacterial Toxins; D009097:Multienzyme Complexes; D014764:Viral Proteins; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex