4OZF

JR5.1 protein complex

Summary for 4OZF

• Entry DOI: 10.2210/pdb4ozf/pdb
• Related: 4OZG 4OZH 4OZI
• Descriptor: HLA class II histocompatibility antigen, DQ alpha 1 chain, HLA class II histocompatibility antigen, DQ beta 1 chain, T-CELL RECEPTOR, JR5.1 ALPHA CHAIN, ... (7 entities in total)
• Functional Keywords: immune receptor-ligand complex, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 97498.26

Authors

Petersen, J.,Reid, H.H.,Rossjohn, J. (deposition date: 2014-02-15, release date: 2014-04-16, Last modification date: 2024-11-20)

Primary citation

Petersen, J.,Montserrat, V.,Mujico, J.R.,Loh, K.L.,Beringer, D.X.,van Lummel, M.,Thompson, A.,Mearin, M.L.,Schweizer, J.,Kooy-Winkelaar, Y.,van Bergen, J.,Drijfhout, J.W.,Kan, W.T.,La Gruta, N.L.,Anderson, R.P.,Reid, H.H.,Koning, F.,Rossjohn, J.
T-cell receptor recognition of HLA-DQ2-gliadin complexes associated with celiac disease.
Nat.Struct.Mol.Biol., 21:480-488, 2014

PubMed Abstract: Celiac disease is a T cell-mediated disease induced by dietary gluten, a component of which is gliadin. 95% of individuals with celiac disease carry the HLA (human leukocyte antigen)-DQ2 locus. Here we determined the T-cell receptor (TCR) usage and fine specificity of patient-derived T-cell clones specific for two epitopes from wheat gliadin, DQ2.5-glia-α1a and DQ2.5-glia-α2. We determined the ternary structures of four distinct biased TCRs specific for those epitopes. All three TCRs specific for DQ2.5-glia-α2 docked centrally above HLA-DQ2, which together with mutagenesis and affinity measurements provided a basis for the biased TCR usage. A non-germline encoded arginine residue within the CDR3β loop acted as the lynchpin within this common docking footprint. Although the TCRs specific for DQ2.5-glia-α1a and DQ2.5-glia-α2 docked similarly, their interactions with the respective gliadin determinants differed markedly, thereby providing a basis for epitope specificity.

PubMed: 24777060
DOI: 10.1038/nsmb.2817

Experimental method

X-RAY DIFFRACTION (2.7 Å)