1h15
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The multiple sclerosis (MS)-associated HLA major histocompatibility | + | 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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Andersson, C.]] | [[Category: Andersson, C.]] | ||
| - | [[Category: Bell, J | + | [[Category: Bell, J I.]] |
[[Category: Fugger, L.]] | [[Category: Fugger, L.]] | ||
[[Category: Harlos, K.]] | [[Category: Harlos, K.]] | ||
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[[Category: Ikemizu, S.]] | [[Category: Ikemizu, S.]] | ||
[[Category: Jacobsen, H.]] | [[Category: Jacobsen, H.]] | ||
| - | [[Category: Jones, E | + | [[Category: Jones, E Y.]] |
[[Category: Lang, H.]] | [[Category: Lang, H.]] | ||
[[Category: Madsen, L.]] | [[Category: Madsen, L.]] | ||
[[Category: Sondergaard, L.]] | [[Category: Sondergaard, L.]] | ||
| - | [[Category: Stuart, D | + | [[Category: Stuart, D I.]] |
[[Category: Svejgaard, A.]] | [[Category: Svejgaard, A.]] | ||
[[Category: Wucherpfennig, K.]] | [[Category: Wucherpfennig, K.]] | ||
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[[Category: peptide]] | [[Category: peptide]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:56:14 2008'' |
Revision as of 10:56, 21 February 2008
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X-RAY CRYSTAL STRUCTURE OF HLA-DRA1*0101/DRB5*0101 COMPLEXED WITH A PEPTIDE FROM EPSTEIN BARR VIRUS DNA POLYMERASE
Overview
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.
About this Structure
1H15 is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as DNA-directed DNA polymerase, with EC number 2.7.7.7 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
A functional and structural basis for TCR cross-reactivity in multiple sclerosis., Lang HL, Jacobsen H, Ikemizu S, Andersson C, Harlos K, Madsen L, Hjorth P, Sondergaard L, Svejgaard A, Wucherpfennig K, Stuart DI, Bell JI, Jones EY, Fugger L, Nat Immunol. 2002 Oct;3(10):940-3. Epub 2002 Sep 3. PMID:12244309
Page seeded by OCA on Thu Feb 21 12:56:14 2008
Categories: DNA-directed DNA polymerase | Homo sapiens | Protein complex | Andersson, C. | Bell, J I. | Fugger, L. | Harlos, K. | Hjorth, P. | Ikemizu, S. | Jacobsen, H. | Jones, E Y. | Lang, H. | Madsen, L. | Sondergaard, L. | Stuart, D I. | Svejgaard, A. | Wucherpfennig, K. | NAG | NDG | Class ii | Dna polymerase | Dna-directed dna polymerase | Dr2 | Drb5 | Ebv | Hla | Immune system | Mhc | Peptide
