PDBsum entry 4gg8

Immune system

PDB id: 4gg8

Contents

Protein chains

174 a.a.

244 a.a.

Ligands

GLC-FRU ×2

PDB id:

4gg8

Name:

Immune system

Title:

Immune receptor

Structure:

T-cell receptor, sp3.4 alpha chain. Chain: e, a. Fragment: extracellular domains. Engineered: yes. Mutation: yes. T-cell receptor, sp3.4 beta chain. Chain: f, b. Fragment: extracellular domains. Engineered: yes.

Source:

Homo sapiens. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

3.20Å R-factor: 0.265 R-free: 0.308

Authors:

S.E.Broughton,A.Theodossis,J.Petersen,H.H.Reid,J.Rossjohn

Key ref:

S.E.Broughton et al. (2012). Biased T cell receptor usage directed against human leukocyte antigen DQ8-restricted gliadin peptides is associated with celiac disease. Immunity, 37, 611-621. PubMed id: 23063329

Date:

06-Aug-12 Release date: 24-Oct-12

Protein chains

K7N5N2  (K7N5N2_HUMAN) -  T-cell receptor, sp3.4 alpha chain from Homo sapiens

Seq: 207 a.a.

Struc: 174 a.a.

Protein chains

P01850  (TRBC1_HUMAN) -  T cell receptor beta constant 1 from Homo sapiens

Seq: 176 a.a.

Struc: 244 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Immunity 37:611-621 (2012)

PubMed id: 23063329

Biased T cell receptor usage directed against human leukocyte antigen DQ8-restricted gliadin peptides is associated with celiac disease.

S.E.Broughton, J.Petersen, A.Theodossis, S.W.Scally, K.L.Loh, A.Thompson, J.van Bergen, Y.Kooy-Winkelaar, K.N.Henderson, T.Beddoe, J.A.Tye-Din, S.I.Mannering, A.W.Purcell, J.McCluskey, R.P.Anderson, F.Koning, H.H.Reid, J.Rossjohn.

ABSTRACT

Celiac disease is a human leukocyte antigen (HLA)-DQ2- and/or DQ8-associated T cell-mediated disorder that is induced by dietary gluten. Although it is established how gluten peptides bind HLA-DQ8 and HLA-DQ2, it is unclear how such peptide-HLA complexes are engaged by the T cell receptor (TCR), a recognition event that triggers disease pathology. We show that biased TCR usage (TRBV9(∗)01) underpins the recognition of HLA-DQ8-α-I-gliadin. The structure of a prototypical TRBV9(∗)01-TCR-HLA-DQ8-α-I-gliadin complex shows that the TCR docks centrally above HLA-DQ8-α-I-gliadin, in which all complementarity-determining region-β (CDRβ) loops interact with the gliadin peptide. Mutagenesis at the TRBV9(∗)01-TCR-HLA-DQ8-α-I-gliadin interface provides an energetic basis for the Vβ bias. Moreover, CDR3 diversity accounts for TRBV9(∗)01(+) TCRs exhibiting differing reactivities toward the gliadin epitopes at various deamidation states. Accordingly, biased TCR usage is an important factor in the pathogenesis of DQ8-mediated celiac disease.