4GG6

Protein complex

Summary for 4GG6

• Entry DOI: 10.2210/pdb4gg6/pdb
• Descriptor: HLA class II histocompatibility antigen, DQ alpha 1 chain, HLA class II histocompatibility antigen, DQ beta 1 chain, T-CELL RECEPTOR, SP3.4 ALPHA CHAIN, ... (6 entities in total)
• Functional Keywords: immune receptor-ligand complex, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 198837.25

Authors

Broughton, S.E.,Theodossis, A.,Petersen, J.,Reid, H.H.,Rossjohn, J. (deposition date: 2012-08-06, release date: 2012-10-24, Last modification date: 2024-11-13)

Primary citation

Broughton, S.E.,Petersen, J.,Theodossis, A.,Scally, S.W.,Loh, K.L.,Thompson, A.,van Bergen, J.,Kooy-Winkelaar, Y.,Henderson, K.N.,Beddoe, T.,Tye-Din, J.A.,Mannering, S.I.,Purcell, A.W.,McCluskey, J.,Anderson, R.P.,Koning, F.,Reid, H.H.,Rossjohn, J.
Biased T cell receptor usage directed against human leukocyte antigen DQ8-restricted gliadin peptides is associated with celiac disease.
Immunity, 37:611-621, 2012

PubMed 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.

PubMed: 23063329
DOI: 10.1016/j.immuni.2012.07.013

Experimental method

X-RAY DIFFRACTION (3.2 Å)