[Molecular mechanism of immunological recognition and the abnormality].
Processing of non-self antigens is an initial step in the sequential immunoreactive system. However, the mechanism of the processing of endogenous antigens, which is presented with MHC (major histocompatibility complex)-class I molecules, has been remained without clarifying. Recently, proteasomes, functioning as a non-lysosomal, ATP/ubiquitin-dependent protease to degrade unnecessary proteins selectively, are thought to be a processing enzyme complex responsible for MHC class I-restricted antigen presentation. A major immunomodulatory cytokine, gamma-interferon (gamma-IFN), was found to regulate this processing system through two distinct mechanisms. First, gamma-IFN induced replacements of the proteasomal subunits X, Y and Z by LMP7, LMP2 and LMP10, respectively, producing "immunoproteasomes" that perhaps function more appropriate for the immunological processing of endogenous antigens. Second, the newly-identified proteasome activator, termed PA28, was induced greatly by gamma-IFN. A relationship between the antigen presentation pathway and its abnormality is also discussed.
Tanaka
K
K
Tokyo Metropolitan Institute of Medical Science/CREST, Japan Science and Technology Corporation (JST).
D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D009097:Multienzyme Complexes / Q000276:immunology / Q000502:physiology; D046988:Proteasome Endopeptidase Complex; D014452:Ubiquitins
D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D014452:Ubiquitins; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex