Proteasome and peptidase function in MHC-class-I-mediated antigen presentation.
MHC-class-I-presented peptides are predominantly generated by the proteasome system. IFN-gamma strongly influences the processing efficiency by inducing immunoproteasome formation and proteasome activator PA28 synthesis. Depending on the protein substrate, the presence of immunoproteasomes and PA28 influence epitope liberation either positively or negatively. Abundantly occurring defective ribosomal products are a major source for proteasome-dependent antigen processing; however, antigen presentation is relatively inefficient. This is in part due to the existence of a panel of cytosolic aminopeptidases, such as bleomycin hydrolase (BH), puromycin-sensitive aminopeptidase (PSA) and thimet oligoendopeptidase (TOP), that can destroy epitopes or their precursors. Other aminopeptidases, such as leucine aminopeptidase (LAP) and endoplasmic reticulum aminopeptidase 1 (ERAP 1), can trim epitope precursors from the amino terminus to their correct size for MHC class I binding to enhance antigen presentation. Recent evidence suggests that tripeptidyl peptidase II (TPPII), a large peptidase with exo-and endo-proteolytic activities, is also involved in antigen processing and may generate a specific set of MHC class I epitopes.
Kloetzel
Peter Michael
PM
Institut für Biochemie, Charité-Medizinische Fakultät der Humboldt Universität zu Berlin, Monbijoustrasse 2, 10117 Berlin, Germany. p-m.Kloetzel@charite.de
Ossendorp
Ferry
F
D000626:Aminopeptidases / Q000502:physiology*; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology; D009097:Multienzyme Complexes / Q000378:metabolism*; D009124:Muscle Proteins / Q000502:physiology; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000502:physiology
D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D011506:Proteins; D007371:Interferon-gamma; D000626:Aminopeptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex