Imperial College London

ProfessorGavinScreaton

Faculty of MedicineDepartment of Immunology and Inflammation

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 1190g.screaton Website

 
 
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Assistant

 

Ms Claire Puddephatt +44 (0)20 7594 1190

 
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Location

 

2.15Faculty BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Culshaw:2017:10.1038/ni.3850,
author = {Culshaw, A and Ladell, K and Gras, S and McLaren, JE and Miners, KL and Farenc, C and van, den Heuvel H and Gostick, E and Dejnirattisai, W and Wangteeraprasert, A and Duangchinda, T and Chotiyarnwong, P and Limpitikul, W and Vasanawathana, S and Malasit, P and Dong, T and Rossjohn, J and Mongkolsapaya, J and Price, DA and Screaton, GR},
doi = {10.1038/ni.3850},
journal = {Nature Immunology},
pages = {1228--1237},
title = {Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8(+) T cell response.},
url = {http://dx.doi.org/10.1038/ni.3850},
volume = {18},
year = {2017}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - 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)-A11:01-restricted CD8(+) T cell populations specific for variants of the nonstructural protein epitope NS3133 that characterize the serotypes DENV1, DENV3 and DENV4. In contrast, the NS3133-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.
AU - Culshaw,A
AU - Ladell,K
AU - Gras,S
AU - McLaren,JE
AU - Miners,KL
AU - Farenc,C
AU - van,den Heuvel H
AU - Gostick,E
AU - Dejnirattisai,W
AU - Wangteeraprasert,A
AU - Duangchinda,T
AU - Chotiyarnwong,P
AU - Limpitikul,W
AU - Vasanawathana,S
AU - Malasit,P
AU - Dong,T
AU - Rossjohn,J
AU - Mongkolsapaya,J
AU - Price,DA
AU - Screaton,GR
DO - 10.1038/ni.3850
EP - 1237
PY - 2017///
SN - 1529-2908
SP - 1228
TI - Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8(+) T cell response.
T2 - Nature Immunology
UR - http://dx.doi.org/10.1038/ni.3850
UR - http://hdl.handle.net/10044/1/52167
VL - 18
ER -