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Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8 + T cell response
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Document Title
Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8 + T cell response
Author
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.
Name from Authors Collection
Affiliations
Department of Medicine, Imperial College London, London, United Kingdom; Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC, Australia; Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand; Pediatric Department, Songkhla Hospital, Ministry of Public Health, Songkhla, Thailand; Pediatric Department, Khon Kaen Hospital, Ministry of Public Health, Khon Kaen, Thailand; Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK, United Kingdom; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States; Naresuan University, Phitsanulok, Thailand; Department of Orthopaedic Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
Type
Article
Source Title
Nature Immunology
ISSN
15292908
Year
2017
Volume
18
Issue
11
Page
1228-1237
Open Access
All Open Access, Green
Publisher
Nature Publishing Group
DOI
10.1038/ni.3850
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 133 that characterize the serotypes DENV1, DENV3 and DENV4. In contrast, the NS3 133 -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. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
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Scopus