Modulation of proteasomal activity required for the generation of a cytotoxic T lymphocyte-defined peptide derived from the tumor antigen MAGE-3
| العنوان: | Modulation of proteasomal activity required for the generation of a cytotoxic T lymphocyte-defined peptide derived from the tumor antigen MAGE-3 |
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| المؤلفون: | Jean Charles Cerottini, Danila Valmori, Uzi Gileadi, Vincenzo Cerundolo, Frédéric Lévy, Pedro Romero, Catherine Servis, P R Dunbar |
| المصدر: | Journal of Experimental Medicine, vol. 189, no. 6, pp. 895-906 The Journal of Experimental Medicine |
| سنة النشر: | 1999 |
| مصطلحات موضوعية: | Proteasome Endopeptidase Complex, endocrine system, Immunology, Lactacystin, Antigen presentation, Peptide, HLA class I molecule, Biology, chemistry.chemical_compound, Antigens, Neoplasm, Multienzyme Complexes, ubiquitin, antigen processing, Tumor Cells, Cultured, Humans, Immunology and Allergy, Cytotoxic T cell, neoplasms, mass spectrometry, chemistry.chemical_classification, Antigen Presentation, Articles, Transfection, Molecular biology, Peptide Fragments, Tumor antigen, Acetylcysteine/analogs & derivatives, Acetylcysteine/pharmacology, Cysteine Endopeptidases/physiology, Multienzyme Complexes/physiology, Neoplasm Proteins/metabolism, Peptide Fragments/metabolism, T-Lymphocytes, Cytotoxic/immunology, Acetylcysteine, Neoplasm Proteins, Cysteine Endopeptidases, CTL, Proteasome, chemistry, melanoma cells, T-Lymphocytes, Cytotoxic |
| الوصف: | We have analyzed the presentation of human histocompatability leukocyte antigen-A*0201–associated tumor peptide antigen MAGE-3271–279 by melanoma cells. We show that specific cytotoxic T lymphocyte (CTL)-recognizing cells transfected with a minigene encoding the preprocessed fragment MAGE-3271–279 failed to recognize cells expressing the full length MAGE-3 protein. Digestion of synthetic peptides extended at the NH2 or COOH terminus of MAGE-3271–279 with purified human proteasome revealed that the generation of the COOH terminus of the antigenic peptide was impaired. Surprisingly, addition of lactacystin to purified proteasome, though partially inhibitory, resulted in the generation of the antigenic peptide. Furthermore, treatment of melanoma cells expressing the MAGE-3 protein with lactacystin resulted in efficient lysis by MAGE-3271–279–specific CTL. We therefore postulate that the generation of antigenic peptides by the proteasome in cells can be modulated by the selective inhibition of certain of its enzymatic activities. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1540-9538 0022-1007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4f79db0e1d0d3c389fa826898dc749ac http://ora.ox.ac.uk/objects/uuid:9ed3513c-d526-4ea5-b8d1-e3c4eddec0a7 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4f79db0e1d0d3c389fa826898dc749ac |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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