Destructive processing by asparagine endopeptidase limits presentation of a dominant T cell epitope in MBP
| العنوان: | Destructive processing by asparagine endopeptidase limits presentation of a dominant T cell epitope in MBP |
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| المؤلفون: | David C. Wraith, Lars Fugger, Graziella Mazza, Streeter Heather Barbara, Daniela Mazzeo, Ponsford Mary, Bénédicte Manoury, Nick J. Viner, Colin Watts |
| المصدر: | Nature Immunology. 3:169-174 |
| بيانات النشر: | Springer Science and Business Media LLC, 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | T cell, Molecular Sequence Data, Immunology, Antigen presentation, Thymus Gland, Biology, Epitope, Mice, medicine, Animals, Humans, Immunology and Allergy, Methaqualone, Amino Acid Sequence, HLA-DR2 Antigen, Asparagine, Antigen Presentation, Mice, Inbred BALB C, Immunodominant Epitopes, Myelin Basic Protein, Molecular biology, Cysteine protease, Peptide Fragments, Endopeptidase, Myelin basic protein, Cysteine Endopeptidases, medicine.anatomical_structure, biology.protein, Central tolerance |
| الوصف: | Little is known about the processing of putative human autoantigens and why tolerance is established to some T cell epitopes but not others. Here we show that a principal human HLA-DR2-restricted epitope--amino acids 85-99 of myelin basic protein, MBP(85-99)--contains a processing site for the cysteine protease asparagine endopeptidase (AEP). Presentation of this epitope by human antigen-presenting cells is inversely proportional to the amount of cellular AEP activity: inhibition of AEP in living cells greatly enhances presentation of the MBP(85-99) epitope, whereas overexpression of AEP diminishes presentation. These results indicate that central tolerance to this encephalitogenic MBP epitope may not be established because destructive processing limits its display in the thymus. Consistent with this hypothesis, AEP is expressed abundantly in thymic antigen-presenting cells. |
| تدمد: | 1529-2916 1529-2908 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d522d5e1039e968de044ee5796148b52 https://doi.org/10.1038/ni754 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d522d5e1039e968de044ee5796148b52 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15292916 15292908 |
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