5WJL

Crystal Structure of HLA-A*11:01 with GTS1 peptide

Summary for 5WJL

• Entry DOI: 10.2210/pdb5wjl/pdb
• Descriptor: HLA class I histocompatibility antigen, A-11 alpha chain, Beta-2-microglobulin, GTS1 peptide, ... (5 entities in total)
• Functional Keywords: hla, tcr, dengue, cd8 t cells, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P13746; Secreted . Note=(Microbial infection) In the presence of M: P61769
• Total number of polymer chains: 9
• Total formula weight: 133886.47

Authors

Gras, S.,Rossjohn, J. (deposition date: 2017-07-23, release date: 2017-09-20, Last modification date: 2024-10-09)

Primary citation

Culshaw, A.,Ladell, K.,Gras, S.,McLaren, J.E.,Miners, K.L.,Farenc, C.,van den Heuvel, H.,Gostick, E.,Dejnirattisai, W.,Wangteeraprasert, A.,Duangchinda, T.,Chotiyarnwong, P.,Limpitikul, W.,Vasanawathana, S.,Malasit, P.,Dong, T.,Rossjohn, J.,Mongkolsapaya, J.,Price, D.A.,Screaton, G.R.
Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8(+) T cell response.
Nat. Immunol., 18:1228-1237, 2017

PubMed Abstract: Adaptive immune responses protect against infection with dengue virus (DENV), yet cross-reactivity with distinct serotypes can precipitate life-threatening clinical disease. We found that clonotypes expressing the T cell antigen receptor (TCR) β-chain variable region 11 (TRBV11-2) were 'preferentially' activated and mobilized within immunodominant human-leukocyte-antigen-(HLA)-A*11:01-restricted CD8 T cell populations specific for variants of the nonstructural protein epitope NS3 that characterize the serotypes DENV1, DENV3 and DENV4. In contrast, the NS3-DENV2-specific repertoire was largely devoid of such TCRs. Structural analysis of a representative TRBV11-2 TCR demonstrated that cross-serotype reactivity was governed by unique interplay between the variable antigenic determinant and germline-encoded residues in the second β-chain complementarity-determining region (CDR2β). Extensive mutagenesis studies of three distinct TRBV11-2 TCRs further confirmed that antigen recognition was dependent on key contacts between the serotype-defined peptide and discrete residues in the CDR2β loop. Collectively, these data reveal an innate-like mode of epitope recognition with potential implications for the outcome of sequential exposure to heterologous DENVs.

PubMed: 28945243
DOI: 10.1038/ni.3850

Experimental method

X-RAY DIFFRACTION (3.15 Å)