Destructive cleavage of antigenic peptides either by the immunoproteasome or by the standard proteasome results in differential antigen presentation

Details

Serval ID
serval:BIB_295276F73668
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Destructive cleavage of antigenic peptides either by the immunoproteasome or by the standard proteasome results in differential antigen presentation
Journal
Journal of Immunology
Author(s)
Chapiro  J., Claverol  S., Piette  F., Ma  W., Stroobant  V., Guillaume  B., Gairin  J. E., Morel  S., Burlet-Schiltz  O., Monsarrat  B., Boon  T., Van den Eynde  B. J.
ISSN
0022-1767 (Print)
Publication state
Published
Issued date
01/2006
Volume
176
Number
2
Pages
1053-61
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan 15
Abstract
The immunoproteasome (IP) is usually viewed as favoring the production of antigenic peptides presented by MHC class I molecules, mainly because of its higher cleavage activity after hydrophobic residues, referred to as the chymotrypsin-like activity. However, some peptides have been found to be better produced by the standard proteasome. The mechanism of this differential processing has not been described. By studying the processing of three tumor antigenic peptides of clinical interest, we demonstrate that their differential processing mainly results from differences in the efficiency of internal cleavages by the two proteasome types. Peptide gp100(209-217) (ITDQVPSFV) and peptide tyrosinase369-377 (YMDGTMSQV) are destroyed by the IP, which cleaves after an internal hydrophobic residue. Conversely, peptide MAGE-C2(336-344) (ALKDVEERV) is destroyed by the standard proteasome by internal cleavage after an acidic residue, in line with its higher postacidic activity. These results indicate that the IP may destroy some antigenic peptides due to its higher chymotrypsin-like activity, rather than favor their production. They also suggest that the sets of peptides produced by the two proteasome types differ more than expected. Considering that mature dendritic cells mainly contain IPs, our results have implications for the design of immunotherapy strategies.
Keywords
Amino Acid Sequence *Antigen Presentation Antigens/genetics/*metabolism Antigens, Neoplasm Binding Sites Cell Line Dendritic Cells/enzymology/immunology Humans Membrane Glycoproteins/genetics/metabolism Molecular Sequence Data Monophenol Monooxygenase/genetics/metabolism Neoplasm Proteins/genetics/metabolism Oligopeptides/genetics/*immunology/*metabolism Peptide Fragments/genetics/immunology/metabolism Proteasome Endopeptidase Complex/*immunology/*metabolism
Pubmed
Web of science
Create date
28/01/2008 9:36
Last modification date
20/08/2019 13:09
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