[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.