5KSB

T15-DQ8.5-glia-gamma1 complex

Summary for 5KSB

• Entry DOI: 10.2210/pdb5ksb/pdb
• Related: 5KS9 5KSA
• Descriptor: HLA class II histocompatibility antigen, DQ alpha 1 chain, HLA class II histocompatibility antigen, DQ beta 1 chain, T15 TCR alpha TRAV20*02, ... (8 entities in total)
• Functional Keywords: celiac disease t cell receptor peptide mhc complex, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 199426.46

Authors

Petersen, J.,Rossjohn, J.,Reid, H.H. (deposition date: 2016-07-08, release date: 2016-09-21, Last modification date: 2020-07-29)

Primary citation

Petersen, J.,Kooy-Winkelaar, Y.,Loh, K.L.,Tran, M.,van Bergen, J.,Koning, F.,Rossjohn, J.,Reid, H.H.
Diverse T Cell Receptor Gene Usage in HLA-DQ8-Associated Celiac Disease Converges into a Consensus Binding Solution.
Structure, 24:1643-1657, 2016

PubMed Abstract: In HLA-DQ8-associated celiac disease, TRAV26-2-TRBV9 and TRAV8-3-TRBV6 T cells recognize the immunodominant DQ8-glia-α1 epitope, whereupon a non-germline-encoded arginine residue played a key role in binding HLA-DQ8-glia-α1. Whether distinct T cell receptor (TCR) recognition modes exist for gliadin epitopes remains unclear. TCR repertoire analysis revealed populations of HLA-DQ8-glia-α1 and HLA-DQ8.5-glia-γ1 restricted TRAV20-TRBV9 T cells that did not possess a non-germline-encoded arginine residue. The crystal structures of a TRAV20-TRBV9 TCR-HLA-DQ8-glia-α1 complex and two TRAV20-TRBV9 TCR-HLA-DQ8.5-glia-γ1 complexes were determined. This revealed that the differential specificity toward DQ8-glia-α1 and DQ8.5-glia-γ1 was governed by CDR3β-loop-mediated interactions. Surprisingly, a germline-encoded arginine residue within the CDR1α loop of the TRAV20 TCR substituted for the role of the non-germline-encoded arginine in the TRAV26-2-TRBV9 and TRAV8-3-TRBV6 TCRs. Thus, in celiac disease, the responding TCR repertoire is driven by a common mechanism that selects for structural elements within the TCR that have convergent binding solutions in HLA-DQ8-gliadin recognition.

PubMed: 27568928
DOI: 10.1016/j.str.2016.07.010

Experimental method

X-RAY DIFFRACTION (2.9 Å)