Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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 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.

Original publication

DOI

10.1038/ni.3850

Type

Journal article

Journal

Nat Immunol

Publication Date

11/2017

Volume

18

Pages

1228 - 1237

Keywords

Adaptive Immunity, Amino Acid Sequence, CD8-Positive T-Lymphocytes, Complementarity Determining Regions, Cross Reactions, Dengue, Dengue Virus, Epitopes, T-Lymphocyte, Germ-Line Mutation, HLA-A Antigens, Humans, Models, Molecular, Protein Structure, Tertiary, Receptors, Antigen, T-Cell, alpha-beta, Serine Endopeptidases, Serotyping, Surface Plasmon Resonance