title: Proteasome isoforms exhibit only quantitative differences in cleavage and epitope generation.
abstract: 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.
authors.affiliation: Institut für Biochemie, Charité - Universitätsmedizin Berlin, Berlin, Germany; Centro Interdipartimentale di Ricerca sul Cancro "Giorgio Prodi,", University of Bologna, Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Mishto
authors.forename: Juliane
authors.initials: J
authors.lastname: Liepe
authors.forename: Kathrin
authors.initials: K
authors.lastname: Textoris-Taube
authors.forename: Christin
authors.initials: C
authors.lastname: Keller
authors.forename: Petra
authors.initials: P
authors.lastname: Henklein
authors.forename: Marion
authors.initials: M
authors.lastname: Weberruß
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Dahlmann
authors.forename: Cordula
authors.initials: C
authors.lastname: Enenkel
authors.forename: Antje
authors.initials: A
authors.lastname: Voigt
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kuckelkorn
authors.forename: Michael P H
authors.initials: MP
authors.lastname: Stumpf
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kloetzel
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D002461:Cell Line, Transformed; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000276:immunology*; D059748:Proteolysis; D013379:Substrate Specificity / Q000235:genetics / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D007527:Isoenzymes; D010455:Peptides; D046988:Proteasome Endopeptidase Complex
keywords: Antigen presentation; Immunoproteasome; MHC class I restricted epitopes; Proteasome; Proteolysis