The production of a new MAGE-3 peptide presented to cytolytic T lymphocytes by HLA-B40 requires the immunoproteasome
| Autor: | V. Russo, Frédéric Lévy, Stéphane Claverol, Pierre van der Bruggen, Erwin S. Schultz, Guy Warnier, Odile Burlet-Schiltz, Sandra Morel, Jacques Chapiro, Thierry Boon, Christophe Lurquin, Benoît Van den Eynde |
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| Přispěvatelé: | UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique |
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Cytotoxicity
Immunologic tumor Proteasome Endopeptidase Complex Immunology Antigen presentation Molecular Sequence Data Clone (cell biology) Peptide Biology 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 Transfection Adenoviridae Beta5i Antigen Antigens Neoplasm Multienzyme Complexes Tumor Cells Cultured Immunology and Allergy Cytotoxic T cell Animals Humans Amino Acid Sequence Peptide sequence mass spectrometry chemistry.chemical_classification Antigen Presentation Tumor Proteasome Mass spectrometry HLA-B40 Antigen HLA-B40 Dendritic Cells β5i Molecular biology Peptide Fragments Clone Cells Neoplasm Proteins CTL Cysteine Endopeptidases Protein Subunits proteasome chemistry HLA-B Antigens COS Cells Cytokines Original Article Protein Processing Post-Translational T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Experimental Medicine, Vol. 195, no. 4, p. 391-399 (2002) Journal of Experimental Medicine, vol. 195, no. 4, pp. 391-9 The Journal of Experimental Medicine |
| Popis: | 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-γ. 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 β5i (LMP7) for β5 is necessary and sufficient for producing the peptide, whereas a mutated form of β5i (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. |
| Databáze: | OpenAIRE |
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