Proteasome isoforms exhibit only quantitative differences in cleavage and epitope generation

作者：Mishto Michele^*; Liepe Juliane; Textoris Taube Kathrin; Keller Christin; Henklein Petra; Weberruss Marion; Dahlmann Burkhardt; Enenkel Cordula; Voigt Antje; Kuckelkorn Ulrike; Stumpf Michael P H; Kloetzel Peter M

来源：European Journal of Immunology, 2014, 44(12): 3508-3521.

DOI：10.1002/eji.201444902

• Antigen presentation
• Immunoproteasome
• MHC class I restricted epitopes
• Proteasome
• Proteolysis

Immunoproteasomes are considered to be optimised to process Ags and to alter the peptide repertoire by generating a qualitatively different set of MHC class I epitopes. Whether the immunoproteasome at the biochemical level, influence the quality rather than the quantity of the immuno-genic peptide pool is still unclear. Here, we quantified the cleavage-site usage by human standard-and immunoproteasomes, and proteasomes from immuno-subunit-deficient mice, as well as the peptides generated from model polypeptides. We show in this study that the different proteasome isoforms can exert significant quantitative differences in the cleavage-site usage and MHC class I restricted epitope production. However, independent of the proteasome isoform and substrates studied, no evidence was obtained for the abolishment of the specific cleavage-site usage, or for differences in the quality of the peptides generated. Thus, we conclude that the observed differences in MHC class I restricted Ag presentation between standard- and immunoproteasomes are due to quantitative differences in the proteasome-generated antigenic peptides.

• 出版日期2014-12