Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII.
The proteasome is key in the cascade of proteolytic processing required for the generation of peptides presented at the cell surface to cytotoxic T lymphocytes by major histocompatibility complex class I molecules. Proteasome-dependent epitope processing is greatly improved through the interferon-gamma-induced formation of immunoproteasomes and the activator complex PA28. Tripeptidyl aminopeptidase II also has a strong effect on epitope generation. With its endoproteolytic and exoproteolytic activities, TPPII acts 'downstream' of the proteasome and relies on products released by the proteasome. The antigen-processing cascade involving different proteolytic systems raises anew the question of how antigenic peptides are generated. We therefore revisit the interferon-gamma-induced immune adaptation of the proteasome and attempt to redefine its function in connection with the emerging importance of TPPII.
Kloetzel
Peter M
PM
Institut für Biochemie, University Medical School-Charité, Humboldt Universität Monbijoustr.2, 10117 Berlin, Germany. p-m.kloetzel@charite.de
D000626:Aminopeptidases; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000378:metabolism*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000276:immunology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D012697:Serine Endopeptidases / Q000378:metabolism*
D000941:Antigens; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex