Journal article
Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8 T cell response
A Culshaw, K Ladell, S Gras, JE McLaren, KL Miners, C Farenc, H Van Den Heuvel, E Gostick, W Dejnirattisai, A Wangteeraprasert, T Duangchinda, P Chotiyarnwong, W Limpitikul, S Vasanawathana, P Malasit, T Dong, J Rossjohn, J Mongkolsapaya, DA Price, GR Screaton
Nature Immunology | NATURE PUBLISHING GROUP | Published : 2017
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 ..
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Awarded by Australian Research Council
Funding Acknowledgements
We thank N. Tangthawornchaikul for management of the clinical database; K. Campbell, H. Halim, A. Nguyen and staff at the Monash Macromolecular Crystallization Facility for technical support; and staff at the Australian Synchrotron for assistance with data collection. Supported by the Australian Research Council (S.G. and J.R.), the National Health and Medical Research Council, the National Institute for Health Research, the Thailand National Centre for Genetic Engineering and Biotechnology, the Thailand Tropical Disease Research Program T2 and the Wellcome Trust (D.A.P. and G.R.S.).