A functional and structural basis for TCR cross-reactivity in multiple sclerosis.
The multiple sclerosis (MS)-associated HLA major histocompatibility complex (MHC) class II alleles DRB1*1501, DRB5*0101 and DQB1*0602 are in strong linkage disequilibrium, making it difficult to determine which is the principal MS risk gene. Here we show that together the DRB1 and DRB5 loci may infl...
| Główni autorzy: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Język: | English |
| Wydane: |
2002
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| _version_ | 1826286578711920640 |
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| author | Lang, H Jacobsen, H Ikemizu, S Andersson, C Harlos, K Madsen, L Hjorth, P Sondergaard, L Svejgaard, A Wucherpfennig, K Stuart, D Bell, J Jones, E Fugger, L |
| author_facet | Lang, H Jacobsen, H Ikemizu, S Andersson, C Harlos, K Madsen, L Hjorth, P Sondergaard, L Svejgaard, A Wucherpfennig, K Stuart, D Bell, J Jones, E Fugger, L |
| author_sort | Lang, H |
| collection | OXFORD |
| description | The multiple sclerosis (MS)-associated HLA major histocompatibility complex (MHC) class II alleles DRB1*1501, DRB5*0101 and DQB1*0602 are in strong linkage disequilibrium, making it difficult to determine which is the principal MS risk gene. Here we show that together the DRB1 and DRB5 loci may influence susceptibility to MS. We demonstrate that a T cell receptor (TCR) from an MS patient recognized both a DRB1*1501-restricted myelin basic protein (MBP) and DRB5*0101-restricted Epstein-Barr virus (EBV) peptide. Crystal structure determination of the DRB5*0101-EBV peptide complex revealed a marked degree of structural equivalence to the DRB1*1501-MBP peptide complex at the surface presented for TCR recognition. This provides structural evidence for molecular mimicry involving HLA molecules. The structural details suggest an explanation for the preponderance of MHC class II associations in HLA-associated diseases. |
| first_indexed | 2024-03-07T01:45:49Z |
| format | Journal article |
| id | oxford-uuid:98616148-5671-4fad-b947-f9d80133e48c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:45:49Z |
| publishDate | 2002 |
| record_format | dspace |
| spelling | oxford-uuid:98616148-5671-4fad-b947-f9d80133e48c2022-03-27T00:06:32ZA functional and structural basis for TCR cross-reactivity in multiple sclerosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:98616148-5671-4fad-b947-f9d80133e48cEnglishSymplectic Elements at Oxford2002Lang, HJacobsen, HIkemizu, SAndersson, CHarlos, KMadsen, LHjorth, PSondergaard, LSvejgaard, AWucherpfennig, KStuart, DBell, JJones, EFugger, LThe multiple sclerosis (MS)-associated HLA major histocompatibility complex (MHC) class II alleles DRB1*1501, DRB5*0101 and DQB1*0602 are in strong linkage disequilibrium, making it difficult to determine which is the principal MS risk gene. Here we show that together the DRB1 and DRB5 loci may influence susceptibility to MS. We demonstrate that a T cell receptor (TCR) from an MS patient recognized both a DRB1*1501-restricted myelin basic protein (MBP) and DRB5*0101-restricted Epstein-Barr virus (EBV) peptide. Crystal structure determination of the DRB5*0101-EBV peptide complex revealed a marked degree of structural equivalence to the DRB1*1501-MBP peptide complex at the surface presented for TCR recognition. This provides structural evidence for molecular mimicry involving HLA molecules. The structural details suggest an explanation for the preponderance of MHC class II associations in HLA-associated diseases. |
| spellingShingle | Lang, H Jacobsen, H Ikemizu, S Andersson, C Harlos, K Madsen, L Hjorth, P Sondergaard, L Svejgaard, A Wucherpfennig, K Stuart, D Bell, J Jones, E Fugger, L A functional and structural basis for TCR cross-reactivity in multiple sclerosis. |
| title | A functional and structural basis for TCR cross-reactivity in multiple sclerosis. |
| title_full | A functional and structural basis for TCR cross-reactivity in multiple sclerosis. |
| title_fullStr | A functional and structural basis for TCR cross-reactivity in multiple sclerosis. |
| title_full_unstemmed | A functional and structural basis for TCR cross-reactivity in multiple sclerosis. |
| title_short | A functional and structural basis for TCR cross-reactivity in multiple sclerosis. |
| title_sort | functional and structural basis for tcr cross reactivity in multiple sclerosis |
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