 |
PDBsum entry 4bkl
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
4bkl
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
216 a.a.
|
|
|
|
|
|
|
|
|
|
|
216 a.a.
|
|
|
|
|
|
|
|
|
|
|
25 a.a.
|
|
|
|
|
|
|
|
|
|
|
26 a.a.
|
|
|
|
|
|
|
|
|
|
|
25 a.a.
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Epitope-Specific antibody response is controlled by immunoglobulin V(h) polymorphisms.
|
|
|
Authors
|
|
B.Raposo,
D.Dobritzsch,
C.Ge,
D.Ekman,
B.Xu,
I.Lindh,
M.Förster,
H.Uysal,
K.S.Nandakumar,
G.Schneider,
R.Holmdahl.
|
|
|
Ref.
|
|
J Exp Med, 2014,
211,
405-411.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
Autoantibody formation is essential for the development of certain autoimmune
diseases like rheumatoid arthritis (RA). Anti-type II collagen (CII) antibodies
are found in RA patients; they interact with cartilage in vivo and are often
highly pathogenic in the mouse. Autoreactivity to CII is directed to multiple
epitopes and conserved between mice and humans. We have previously mapped the
antibody response to CII in a heterogeneous stock cohort of mice, with a strong
association with the IgH locus. We positioned the genetic polymorphisms and
determined the structural requirements controlling antibody recognition of one
of the major CII epitopes. Polymorphisms at positions S31R and W33T of the
associated variable heavy chain (VH) allele were identified and confirmed by
gene sequencing. The Fab fragment binding the J1 epitope was crystallized, and
site-directed mutagenesis confirmed the importance of those two variants for
antigen recognition. Back mutation to germline sequence provided evidence for a
preexisting recognition of the J1 epitope. These data demonstrate a genetic
association of epitope-specific antibody responses with specific VH alleles, and
it highlights the importance of germline-encoded antibodies in the pathogenesis
of antibody-mediated autoimmune diseases.
|
|
|
|
|
|
|
