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Title: Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8 + T cell response
Authors: Abigail Culshaw
Kristin Ladell
Stephanie Gras
James E. McLaren
Kelly L. Miners
Carine Farenc
Heleen Van Den Heuvel
Emma Gostick
Wanwisa Dejnirattisai
Apirath Wangteeraprasert
Thaneeya Duangchinda
Pojchong Chotiyarnwong
Wannee Limpitikul
Sirijitt Vasanawathana
Prida Malasit
Tao Dong
Jamie Rossjohn
Juthathip Mongkolsapaya
David A. Price
Gavin R. Screaton
Imperial College London
Cardiff University
Monash University
Thailand National Center for Genetic Engineering and Biotechnology
Songkhla Hospital
Khon Kaen Regional Hospital
Mahidol University
Weatherall Institute of Molecular Medicine
National Institute of Allergy and Infectious Diseases
Naresuan University
Keywords: Immunology and Microbiology
Issue Date: 18-Oct-2017
Citation: Nature Immunology. Vol.18, No.11 (2017), 1228-1237
Abstract: © 2017 Nature America, Inc., part of Springer Nature. All rights reserved. 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.
ISSN: 15292916
Appears in Collections:Scopus 2016-2017

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