A ROLE FOR THE UBIQUITIN-DEPENDENT PROTEOLYTIC PATHWAY IN MHC CLASS I-RESTRICTED ANTIGEN PRESENTATION

THE degradation of most cellular proteins starts with their covalent c onjugation with ubiquitin1,2. This labels the proteins for rapid hydro lysis to oligopeptides by a (26S) proteolytic complex containing a (20 S) degradative particle called the proteasome3,4. Some system in the c ytosol also generates antigenic peptides from endogenously synthesized cellular and viral proteins5-10. These peptides bind to newly synthes ized class I major histocompatibility complex molecules in the endopla smic reticulum and peptide/class I complexes are then transported to t he cell surface for presentation to cytotoxic T cells11,12. How these peptides are produced is unknown, although a modification that promote s ubiquitin-dependent degradation of a viral protein enhances its pres entation with class I13 and indirect evidence suggests a role for prot eolytic particles closely resembling and perhaps identical to the prot easome4,12,14,15. Using cells that exhibit a temperature-sensitive def ect in ubiquitin conjugation, we report here that nonpermissive temper ature inhibited class I-restricted presentation of ovalbumin introduce d into the cytosol, but did not affect presentation of an ovalbumin pe ptide synthesized from a minigene. These results implicate the ubiquit in-dependent proteolytic pathway in the production of antigenic peptid es.