T cell receptor alpha variable 12-2 bias in the immunodominant response to Yellow fever virus.

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State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_47E01B2BD815
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
T cell receptor alpha variable 12-2 bias in the immunodominant response to Yellow fever virus.
Journal
European journal of immunology
Author(s)
Bovay A., Zoete V., Dolton G., Bulek A.M., Cole D.K., Rizkallah P.J., Fuller A., Beck K., Michielin O., Speiser D.E., Sewell A.K., Fuertes Marraco S.A.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Publication state
Published
Issued date
02/2018
Peer-reviewed
Oui
Volume
48
Number
2
Pages
258-272
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The repertoire of human αβ T-cell receptors (TCRs) is generated via somatic recombination of germline gene segments. Despite this enormous variation, certain epitopes can be immunodominant, associated with high frequencies of antigen-specific T cells and/or exhibit bias toward a TCR gene segment. Here, we studied the TCR repertoire of the HLA-A*0201-restricted epitope LLWNGPMAV (hereafter, A2/LLW) from Yellow Fever virus, which generates an immunodominant CD8 <sup>+</sup> T cell response to the highly effective YF-17D vaccine. We discover that these A2/LLW-specific CD8 <sup>+</sup> T cells are highly biased for the TCR α chain TRAV12-2. This bias is already present in A2/LLW-specific naïve T cells before vaccination with YF-17D. Using CD8 <sup>+</sup> T cell clones, we show that TRAV12-2 does not confer a functional advantage on a per cell basis. Molecular modeling indicated that the germline-encoded complementarity determining region (CDR) 1α loop of TRAV12-2 critically contributes to A2/LLW binding, in contrast to the conventional dominant dependence on somatically rearranged CDR3 loops. This germline component of antigen recognition may explain the unusually high precursor frequency, prevalence and immunodominance of T-cell responses specific for the A2/LLW epitope.
Keywords
Adaptive Immunity/genetics, CD8-Positive T-Lymphocytes/physiology, Cell Line, Clonal Selection, Antigen-Mediated, Clone Cells, Complementarity Determining Regions/genetics, Cytotoxicity, Immunologic, Epitopes, T-Lymphocyte/metabolism, HLA-A2 Antigen/metabolism, Humans, Immunodominant Epitopes/metabolism, Lymphocyte Activation, Receptors, Antigen, T-Cell, alpha-beta/genetics, T-Cell Antigen Receptor Specificity, Viral Proteins/metabolism, Viral Vaccines/immunology, Yellow Fever/genetics, Yellow Fever/immunology, Yellow fever virus/physiology, Antigen recognition, Germline, T cell receptor Alpha Variable (TRAV)-12-2, T cell receptor bias, Yellow Fever virus
Pubmed
Web of science
Open Access
Yes
Create date
09/10/2017 12:38
Last modification date
20/08/2019 13:54
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