The production of a new MAGE-3 peptide presented to cytolytic T lymphocytes by HLA-B40 requires the immunoproteasome

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Serval ID
serval:BIB_BE0BA2FC3897
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The production of a new MAGE-3 peptide presented to cytolytic T lymphocytes by HLA-B40 requires the immunoproteasome
Journal
Journal of Experimental Medicine
Author(s)
Schultz  E. S., Chapiro  J., Lurquin  C., Claverol  S., Burlet-Schiltz  O., Warnier  G., Russo  V., Morel  S., Levy  F., Boon  T., Van den Eynde  B. J., van der Bruggen  P.
ISSN
0022-1007 (Print)
Publication state
Published
Issued date
02/2002
Volume
195
Number
4
Pages
391-9
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb 18
Abstract
By stimulating human CD8(+) T lymphocytes with autologous dendritic cells infected with an adenovirus encoding MAGE-3, we obtained a cytotoxic T lymphocyte (CTL) clone that recognized a new MAGE-3 antigenic peptide, AELVHFLLL, which is presented by HLA-B40. This peptide is also encoded by MAGE-12. The CTL clone recognized MAGE-3--expressing tumor cells only when they were first treated with IFN-gamma. Since this treatment is known to induce the exchange of the three catalytic subunits of the proteasome to form the immunoproteasome, this result suggested that the processing of this MAGE-3 peptide required the immunoproteasome. Transfection experiments showed that the substitution of beta5i (LMP7) for beta5 is necessary and sufficient for producing the peptide, whereas a mutated form of beta5i (LMP7) lacking the catalytically active site was ineffective. Mass spectrometric analyses of in vitro digestions of a long precursor peptide with either proteasome type showed that the immunoproteasome produced the antigenic peptide more efficiently, whereas the standard proteasome more efficiently introduced cleavages destroying the antigenic peptide. This is the first example of a tumor-specific antigen exclusively presented by tumor cells expressing the immunoproteasome.
Keywords
Adenoviridae/genetics Amino Acid Sequence Animals Antigen Presentation Antigens, Neoplasm/chemistry/genetics/*immunology/metabolism COS Cells Clone Cells/enzymology/immunology/metabolism Cysteine Endopeptidases/chemistry/*metabolism Cytokines/immunology Cytotoxicity, Immunologic Dendritic Cells/immunology HLA-B Antigens/*immunology Humans Molecular Sequence Data Multienzyme Complexes/chemistry/*metabolism Neoplasm Proteins/chemistry/genetics/*immunology/*metabolism Peptide Fragments/chemistry/genetics/immunology/metabolism Proteasome Endopeptidase Complex Protein Processing, Post-Translational Protein Subunits T-Lymphocytes, Cytotoxic/*enzymology/*immunology/metabolism Transfection Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:17
Last modification date
20/08/2019 15:32
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