A functional and structural basis for TCR cross-resctivity in multiple sclerosis
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A functional and structural basis for TCR cross-resctivity in multiple sclerosis. / Lang, Heather L.E.; Jacobsen, Helle; Ikemizu, S.; Andersson, Christina; Harlos, Karl; Madsen, L.; Hjorth, Peter; Søndergaard, Leif; Svejgaard, Arne; Wucherpfennig, Kai; Stuart, David I.; Bell, John I.; Jones, Yvonne; Fugger, Lars.
In: Nature Immunology, Vol. 3, No. 10, 2002, p. 940-943.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A functional and structural basis for TCR cross-resctivity in multiple sclerosis
AU - Lang, Heather L.E.
AU - Jacobsen, Helle
AU - Ikemizu, S.
AU - Andersson, Christina
AU - Harlos, Karl
AU - Madsen, L.
AU - Hjorth, Peter
AU - Søndergaard, Leif
AU - Svejgaard, Arne
AU - Wucherpfennig, Kai
AU - Stuart, David I.
AU - Bell, John I.
AU - Jones, Yvonne
AU - Fugger, Lars
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
U2 - 10.1038/ni835
DO - 10.1038/ni835
M3 - Journal article
VL - 3
SP - 940
EP - 943
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 10
ER -
ID: 134822