 |
PDBsum entry 4z7v
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
4z7v
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
180 a.a.
|
|
|
|
|
|
|
|
|
|
|
172 a.a.
|
|
|
|
|
|
|
|
|
|
|
199 a.a.
|
|
|
|
|
|
|
|
|
|
|
243 a.a.
|
|
|
|
|
|
|
|
|
|
|
13 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Determinants of gliadin-Specific t cell selection in celiac disease.
|
|
|
Authors
|
|
J.Petersen,
J.Van bergen,
K.L.Loh,
Y.Kooy-Winkelaar,
D.X.Beringer,
A.Thompson,
S.F.Bakker,
C.J.Mulder,
K.Ladell,
J.E.Mclaren,
D.A.Price,
J.Rossjohn,
H.H.Reid,
F.Koning.
|
|
|
Ref.
|
|
J Immunol, 2015,
194,
6112-6122.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
In HLA-DQ8-associated celiac disease (CD), the pathogenic T cell response is
directed toward an immunodominant α-gliadin-derived peptide (DQ8-glia-α1).
However, our knowledge of TCR gene usage within the primary intestinal tissue of
HLA-DQ8 (+) CD patients is limited. We identified two populations of
HLA-DQ8-glia-α1 tetramer(+) CD4(+) T cells that were essentially undetectable
in biopsy samples from patients on a gluten-free diet but expanded rapidly and
specifically after antigenic stimulation. Distinguished by expression of TRBV9,
both T cell populations displayed biased clonotypic repertoires and reacted
similarly against HLA-DQ8-glia-α1. In particular, TRBV9 paired most often with
TRAV26-2, whereas the majority of TRBV9(-) TCRs used TRBV6-1 with no clear TRAV
gene preference. Strikingly, both tetramer(+)/TRBV9(+) and tetramer(+)/TRBV9(-)
T cells possessed a non-germline-encoded arginine residue in their CDR3α and
CDR3β loops, respectively. Comparison of the crystal structures of three
TRBV9(+) TCRs and a TRBV9(-) TCR revealed that, as a result of distinct TCR
docking modes, the HLA-DQ8-glia-α1 contacts mediated by the CDR3-encoded
arginine were almost identical between TRBV9(+) and TRBV9(-) TCRs. In all cases,
this interaction centered on two hydrogen bonds with a specific serine residue
in the bound peptide. Replacement of serine with alanine at this position
abrogated TRBV9(+) and TRBV9(-) clonal T cell proliferation in response to
HLA-DQ8-glia-α1. Gluten-specific memory CD4(+) T cells with structurally and
functionally conserved TCRs therefore predominate in the disease-affected tissue
of patients with HLA-DQ8-mediated CD.
|
|
|
|
|
|
|
