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

Autor: Bovay, Amandine, Zoete, Vincent, Dolton, Garry, Bulek, Anna M., Cole, David K., Rizkallah, Pierre J., Fuller, Anna, Beck, Konrad, Michielin, Olivier, Speiser, Daniel E., Sewell, Andrew K., Fuertes Marraco, Silvia A.
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Cytotoxicity
Immunologic
Germline
Receptors
Antigen
T-Cell
alpha-beta
Adaptive immunity
Epitopes
T-Lymphocyte
T-Cell Antigen Receptor Specificity
CD8-Positive T-Lymphocytes
Lymphocyte Activation
Cell Line
Adaptive Immunity/genetics
CD8-Positive T-Lymphocytes/physiology
Clonal Selection
Antigen-Mediated
Clone Cells
Complementarity Determining Regions/genetics
Epitopes
T-Lymphocyte/metabolism
HLA-A2 Antigen/metabolism
Humans
Immunodominant Epitopes/metabolism
Receptors
Antigen
T-Cell
alpha-beta/genetics
Viral Proteins/metabolism
Viral Vaccines/immunology
Yellow Fever/genetics
Yellow Fever/immunology
Yellow fever virus/physiology
Antigen recognition
T cell receptor Alpha Variable (TRAV)-12-2
T cell receptor bias
Yellow Fever virus
Viral Proteins
HLA-A2 Antigen
Yellow Fever
Basic
Research Articles
Immunodominant Epitopes
Viral Vaccines
Complementarity Determining Regions
Research Article|Basic
T cell receptor Alpha Variable (TRAV)‐12‐2
Zdroj: European Journal of Immunology
European journal of immunology, vol. 48, no. 2, pp. 258-272
ISSN: 1521-4141
0014-2980
Popis: 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 + T cell response to the highly effective YF-17D vaccine. We discover that these A2/LLW-specific CD8 + 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 + 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.
Databáze: OpenAIRE
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