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PDBsum entry 4md0
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Immune system
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PDB id
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4md0
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Contents |
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179 a.a.
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189 a.a.
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13 a.a.
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PDB id:
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| Name: |
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Immune system
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Title:
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Immune receptor
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Structure:
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Hla class ii histocompatibility antigen, dr alpha chain. Chain: a. Fragment: extracellular domain, unp residues 26-206. Synonym: mhc class ii antigen dra. Engineered: yes. Hla class ii histocompatibility antigen, drb1-4 beta chain. Chain: b. Fragment: extracellular domain, unp residues 30-219. Synonym: mhc class ii antigen drb1 4, Dr-4, dr4.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-dra, hla-dra1. Expressed in: homo sapiens. Expression_system_taxid: 9606. Gene: hla-drb1. Synthetic: yes. Other_details: this sequence is from human vimentin and contains
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Resolution:
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2.19Å
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R-factor:
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0.176
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R-free:
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0.208
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Authors:
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S.W.Scally,J.Rossjohn
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Key ref:
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S.W.Scally
et al.
(2013).
A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis.
J Exp Med,
210,
2569-2582.
PubMed id:
DOI:
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Date:
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22-Aug-13
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Release date:
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04-Dec-13
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PROCHECK
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Headers
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References
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P01903
(DRA_HUMAN) -
HLA class II histocompatibility antigen, DR alpha chain from Homo sapiens
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Seq:
Struc:
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254 a.a.
179 a.a.
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DOI no:
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J Exp Med
210:2569-2582
(2013)
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PubMed id:
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A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis.
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S.W.Scally,
J.Petersen,
S.C.Law,
N.L.Dudek,
H.J.Nel,
K.L.Loh,
L.C.Wijeyewickrema,
S.B.Eckle,
J.van Heemst,
R.N.Pike,
J.McCluskey,
R.E.Toes,
N.L.La Gruta,
A.W.Purcell,
H.H.Reid,
R.Thomas,
J.Rossjohn.
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ABSTRACT
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Rheumatoid arthritis (RA) is strongly associated with the human leukocyte
antigen (HLA)-DRB1 locus that possesses the shared susceptibility epitope (SE)
and the citrullination of self-antigens. We show how citrullinated aggrecan and
vimentin epitopes bind to HLA-DRB1*04:01/04. Citrulline was accommodated within
the electropositive P4 pocket of HLA-DRB1*04:01/04, whereas the electronegative
P4 pocket of the RA-resistant HLA-DRB1*04:02 allomorph interacted with arginine
or citrulline-containing epitopes. Peptide elution studies revealed P4
arginine-containing peptides from HLA-DRB1*04:02, but not from
HLA-DRB1*04:01/04. Citrullination altered protease susceptibility of vimentin,
thereby generating self-epitopes that are presented to T cells in
HLA-DRB1*04:01(+) individuals. Using HLA-II tetramers, we observed citrullinated
vimentin- and aggrecan-specific CD4(+) T cells in the peripheral blood of
HLA-DRB1*04:01(+) RA-affected and healthy individuals. In RA patients,
autoreactive T cell numbers correlated with disease activity and were deficient
in regulatory T cells relative to healthy individuals. These findings reshape
our understanding of the association between citrullination, the HLA-DRB1 locus,
and T cell autoreactivity in RA.
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Links
