THE CLEAVAGE PREFERENCE OF THE PROTEASOME GOVERNS THE YIELD OF ANTIGENIC PEPTIDES

Proteasomes degrade endogenous proteins in the cytosol. The potential contribution of the proteasome to the effect of flanking sequences on the presentation of an antigenic epitope presented by the major histoc ompatibility complex class I allele L(d) was studied. Peptides generat ed in cells from minigenes coding for peptides of 17- and 19-amino aci d length were compared with the in vitro 20S proteasome degradation pr oducts of the respective synthetic peptides. The quality of generated peptides was independent of ubiquitination. In vivo and in vitro proce ssing products were indistinguishable with respect to peptide size and abundance. Altering the neighboring sequence substantially improved t he yield of the final antigenic nonapeptide by 20S proteasome cleavage . These results suggest that, in addition to the presence of major his tocompatibility complex class I allelic motifs, the cleavage preferenc e of the proteasome can define the antigenic potential of a protein.