Culshaw, Abigail, ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
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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) b-chain variable region 11 (TRBV11-2) were ‘preferentially’ activated and mobilized within immunodominant humanleukocyte- antigen (HLA) A*11:01-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 b-chain complementarity-determining region (CDR2b). 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 CDR2b loop. Collectively, these data reveal an innate-like mode of epitope recognition with potential implications for the outcome of sequential exposure to heterologous DENVs.
Item Type: | Article |
---|---|
Date Type: | Publication |
Status: | Published |
Schools: | Medicine |
Subjects: | R Medicine > R Medicine (General) |
Publisher: | Nature Publishing Group |
ISSN: | 1529-2908 |
Date of First Compliant Deposit: | 31 October 2017 |
Date of Acceptance: | 5 September 2017 |
Last Modified: | 05 Nov 2024 23:46 |
URI: | https://orca.cardiff.ac.uk/id/eprint/106078 |
Citation Data
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