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PDBsum entry 4gg6

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Immune system PDB id
4gg6
Jmol
Contents
Protein chains
180 a.a.
163 a.a.
173 a.a.
187 a.a.
243 a.a.
177 a.a.
13 a.a.
Ligands
NAG ×3

References listed in PDB file
Key reference
Title Biased t cell receptor usage directed against human leukocyte antigen dq8-Restricted gliadin peptides is associated with celiac disease.
Authors 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.
Ref. Immunity, 2012, 37, 611-621. [DOI no: 10.1016/j.immuni.2012.07.013]
PubMed id 23063329
DOI number 10.1016/J.IMMUNI.2012.07.013
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.
PROCHECK
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