T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides.
Environmental factors account for 75% of the risk of developing multiple sclerosis (MS). Numerous infections have been suspected as environmental disease triggers, but none of them has consistently been incriminated, and it is unclear how so many different infections may play a role. We show that a...
| मुख्य लेखकों: | , , , , , , , , , , , , , , , , , , |
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| स्वरूप: | Journal article |
| भाषा: | English |
| प्रकाशित: |
2009
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| _version_ | 1826299196918988800 |
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| author | Harkiolaki, M Holmes, S Svendsen, P Gregersen, J Jensen, LT McMahon, R Friese, M van Boxel, G Etzensperger, R Tzartos, J Kranc, K Sainsbury, S Harlos, K Mellins, E Palace, J Esiri, M Van Der Merwe, P Jones, E Fugger, L |
| author_facet | Harkiolaki, M Holmes, S Svendsen, P Gregersen, J Jensen, LT McMahon, R Friese, M van Boxel, G Etzensperger, R Tzartos, J Kranc, K Sainsbury, S Harlos, K Mellins, E Palace, J Esiri, M Van Der Merwe, P Jones, E Fugger, L |
| author_sort | Harkiolaki, M |
| collection | OXFORD |
| description | Environmental factors account for 75% of the risk of developing multiple sclerosis (MS). Numerous infections have been suspected as environmental disease triggers, but none of them has consistently been incriminated, and it is unclear how so many different infections may play a role. We show that a microbial peptide, common to several major classes of bacteria, can induce MS-like disease in humanized mice by crossreacting with a T cell receptor (TCR) that also recognizes a peptide from myelin basic protein, a candidate MS autoantigen. Structural analysis demonstrates this crossreactivity is due to structural mimicry of a binding hotspot shared by self and microbial antigens, rather than to degenerate TCR recognition. Biophysical studies reveal that the autoreactive TCR binding affinity is markedly lower for the microbial (mimicry) peptide than for the autoantigenic peptide. Thus, these data suggest a possible explanation for the difficulty in incriminating individual infections in the development of MS. |
| first_indexed | 2024-03-07T04:58:14Z |
| format | Journal article |
| id | oxford-uuid:d75c8853-9b6c-4d8e-8c13-aa2a73ce3c3c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:58:14Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:d75c8853-9b6c-4d8e-8c13-aa2a73ce3c3c2022-03-27T08:40:29ZT cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d75c8853-9b6c-4d8e-8c13-aa2a73ce3c3cEnglishSymplectic Elements at Oxford2009Harkiolaki, MHolmes, SSvendsen, PGregersen, JJensen, LTMcMahon, RFriese, Mvan Boxel, GEtzensperger, RTzartos, JKranc, KSainsbury, SHarlos, KMellins, EPalace, JEsiri, MVan Der Merwe, PJones, EFugger, LEnvironmental factors account for 75% of the risk of developing multiple sclerosis (MS). Numerous infections have been suspected as environmental disease triggers, but none of them has consistently been incriminated, and it is unclear how so many different infections may play a role. We show that a microbial peptide, common to several major classes of bacteria, can induce MS-like disease in humanized mice by crossreacting with a T cell receptor (TCR) that also recognizes a peptide from myelin basic protein, a candidate MS autoantigen. Structural analysis demonstrates this crossreactivity is due to structural mimicry of a binding hotspot shared by self and microbial antigens, rather than to degenerate TCR recognition. Biophysical studies reveal that the autoreactive TCR binding affinity is markedly lower for the microbial (mimicry) peptide than for the autoantigenic peptide. Thus, these data suggest a possible explanation for the difficulty in incriminating individual infections in the development of MS. |
| spellingShingle | Harkiolaki, M Holmes, S Svendsen, P Gregersen, J Jensen, LT McMahon, R Friese, M van Boxel, G Etzensperger, R Tzartos, J Kranc, K Sainsbury, S Harlos, K Mellins, E Palace, J Esiri, M Van Der Merwe, P Jones, E Fugger, L T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides. |
| title | T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides. |
| title_full | T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides. |
| title_fullStr | T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides. |
| title_full_unstemmed | T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides. |
| title_short | T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides. |
| title_sort | t cell mediated autoimmune disease due to low affinity crossreactivity to common microbial peptides |
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