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PMID: 7500032 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The cleavage preference of the proteasome governs the yield of antigenic peptides.

The Journal of experimental medicine ·Vol. 182 ·No. 6 ·1995-12-01 ·Pages 1865-70

Eggers M, Boes-Fabian B, Ruppert T, Kloetzel PM, Koszinowski UH

Abstract

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 histocompatibility complex class I allele Ld was studied. Peptides generated in cells from minigenes coding for peptides of 17- and 19-amino acid length were compared with the in vitro 20S proteasome degradation products of the respective synthetic peptides. The quality of generated peptides was independent of ubiquitination. In vivo and in vitro processing products were indistinguishable with respect to peptide size and abundance. Altering the neighboring sequence substantially improved the yield of the final antigenic nonapeptide by 20S proteasome cleavage. These results suggest that, in addition to the presence of major histocompatibility complex class I allelic motifs, the cleavage preference of the proteasome can define the antigenic potential of a protein.

MeSH Terms
Aldehydes Amino Acid Sequence Animals Antigen-Presenting Cells/metabolism Antigens, Viral/chemistry Cells, Cultured Cysteine Endopeptidases/metabolism Cytomegalovirus/immunology Epitope Mapping Mass Spectrometry Mice Mice, Inbred BALB C Molecular Sequence Data Multienzyme Complexes/metabolism Peptides/chemistry,immunology,metabolism Proteasome Endopeptidase Complex Recombinant Proteins Structure-Activity Relationship Substrate Specificity T-Lymphocytes, Cytotoxic/immunology Ubiquitins/metabolism
Chemicals
Aldehydes Antigens, Viral Multienzyme Complexes Peptides Recombinant Proteins Ubiquitins Cysteine Endopeptidases Proteasome Endopeptidase Complex
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Eggers M
Abteilung Virologie, Ruprecht-Karls Universität Heidelberg, Germany.
Boes-Fabian B
Ruppert T
Kloetzel P M
Koszinowski U H
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28 references, click to expand
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.182.6.1865
Published
1995-12-01
Pages
1865-70
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192259
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.182.6.1865 PMC Full Text View journal details
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