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Rapid degradation of a large fraction of newly synthesized proteins by proteasomes 总被引:47,自引:0,他引:47
MHC class I molecules function to present peptides eight to ten residues long to the immune system. These peptides originate primarily from a cytosolic pool of proteins through the actions of proteasomes, and are transported into the endoplasmic reticulum, where they assemble with nascent class I molecules. Most peptides are generated from proteins that are apparently metabolically stable. To explain this, we previously proposed that peptides arise from proteasomal degradation of defective ribosomal products (DRiPs). DRiPs are polypeptides that never attain native structure owing to errors in translation or post-translational processes necessary for proper protein folding. Here we show, first, that DRiPs constitute upwards of 30% of newly synthesized proteins as determined in a variety of cell types; second, that at least some DRiPs represent ubiquitinated proteins; and last, that ubiquitinated DRiPs are formed from human immunodeficiency virus Gag polyprotein, a long-lived viral protein that serves as a source of antigenic peptides. 相似文献
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It has been 15 years since we proposed the defective ribosomal product (DRiP) hypothesis to explain the rapid presentation
of viral peptides by MHC class I molecules on the surface of infected cells. Here, we review the evidence for the contribution
of DRiPs to antigen processing, pointing to the uncertainties regarding the physical nature of DRiPs, and emphasizing recent
findings suggesting that peptide generation is a specialized process involving compartmentalized translation. 相似文献
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Recombinant vaccinia virus primes and stimulates influenza haemagglutinin-specific cytotoxic T cells 总被引:26,自引:0,他引:26
The ability of vaccinia virus to accept and express cloned genes encoding immunologically important proteins of unrelated viruses and malarial parasites has suggested a novel approach to the development of live vaccines. Vaccinia virus recombinants retain infectivity and stimulate synthesis of specific antibodies to the cloned gene products in vaccinated animals. Moreover, animals inoculated with recombinants expressing the influenza virus haemagglutinin (HA), the hepatitis B virus surface antigen, and type 1 herpesvirus glycoprotein D were protected against subsequent challenge with the corresponding virus. For maximal effectiveness, vaccines should produce cellular as well as humoral immunity. We now report that a vaccinia virus recombinant, expressing the influenza HA, primes and stimulates a specific murine cytotoxic T-lymphocyte (CTL) response. Histocompatible cells infected with this recombinant also serve as targets for CTLs. These properties make vaccinia virus a unique tool for studying cell-mediated immunity and enhance the attractiveness of this vector for production of live vaccines. 相似文献
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