4Z7U

S13 complex

Summary for 4Z7U

• Entry DOI: 10.2210/pdb4z7u/pdb
• Related: 4Z7V 4Z7W
• Descriptor: MHC class II HLA-DQ-alpha chain, MHC class II HLA-DQ-beta-1, T-CELL RECEPTOR, S13 ALPHA CHAIN, ... (8 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: 198817.27

Authors

Petersen, J.,Rossjohn, J.,Reid, H.H.,Koning, F. (deposition date: 2015-04-08, release date: 2015-06-03, Last modification date: 2024-11-20)

Primary citation

Petersen, J.,van Bergen, J.,Loh, K.L.,Kooy-Winkelaar, Y.,Beringer, D.X.,Thompson, A.,Bakker, S.F.,Mulder, C.J.,Ladell, K.,McLaren, J.E.,Price, D.A.,Rossjohn, J.,Reid, H.H.,Koning, F.
Determinants of Gliadin-Specific T Cell Selection in Celiac Disease.
J Immunol., 194:6112-6122, 2015

PubMed Abstract: In HLA-DQ8-associated celiac disease (CD), the pathogenic T cell response is directed toward an immunodominant α-gliadin-derived peptide (DQ8-glia-α1). However, our knowledge of TCR gene usage within the primary intestinal tissue of HLA-DQ8 (+) CD patients is limited. We identified two populations of HLA-DQ8-glia-α1 tetramer(+) CD4(+) T cells that were essentially undetectable in biopsy samples from patients on a gluten-free diet but expanded rapidly and specifically after antigenic stimulation. Distinguished by expression of TRBV9, both T cell populations displayed biased clonotypic repertoires and reacted similarly against HLA-DQ8-glia-α1. In particular, TRBV9 paired most often with TRAV26-2, whereas the majority of TRBV9(-) TCRs used TRBV6-1 with no clear TRAV gene preference. Strikingly, both tetramer(+)/TRBV9(+) and tetramer(+)/TRBV9(-) T cells possessed a non-germline-encoded arginine residue in their CDR3α and CDR3β loops, respectively. Comparison of the crystal structures of three TRBV9(+) TCRs and a TRBV9(-) TCR revealed that, as a result of distinct TCR docking modes, the HLA-DQ8-glia-α1 contacts mediated by the CDR3-encoded arginine were almost identical between TRBV9(+) and TRBV9(-) TCRs. In all cases, this interaction centered on two hydrogen bonds with a specific serine residue in the bound peptide. Replacement of serine with alanine at this position abrogated TRBV9(+) and TRBV9(-) clonal T cell proliferation in response to HLA-DQ8-glia-α1. Gluten-specific memory CD4(+) T cells with structurally and functionally conserved TCRs therefore predominate in the disease-affected tissue of patients with HLA-DQ8-mediated CD.

PubMed: 25948817
DOI: 10.4049/jimmunol.1500161

Experimental method

X-RAY DIFFRACTION (2.7 Å)