T cell receptor alpha variable 12-2 bias in the immunodominant response to Yellow fever virus.
T cell receptor alpha variable 12-2 bias in the immunodominant response to Yellow fever virus.
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DOI：
10.1002/eji.201747082
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发表时间：
2018-03
影响因子：
5.4
通讯作者：
Fuertes Marraco SA
中科院分区：
文献类型：
--
作者：
Bovay A;Zoete V;Dolton G;Bulek AM;Cole DK;Rizkallah PJ;Fuller A;Beck K;Michielin O;Speiser DE;Sewell AK;Fuertes Marraco SA
人αβ T细胞受体（TCR）的库是通过生殖系基因片段的体细胞重组产生的。尽管存在这种巨大的变异，但某些表位可能是免疫显性的，与高频率的抗原特异性T细胞相关和/或表现出对TCR基因片段的偏好。在这里，我们研究了黄热病病毒的HLA-A *0201限制性表位LLWNGPMAV（以下简称A2/LLW）的TCR库，该表位对高效的YF-17 D疫苗产生免疫显性CD 8 + T细胞应答。我们发现这些A2/LLW特异性CD 8 + T细胞对TCR α链TRAV 12 - 2具有高度偏好。在接种YF-17 D之前，这种偏倚已经存在于A2/LLW特异性幼稚T细胞中。使用CD 8 + T细胞克隆，我们表明TRAV 12 - 2不会在每个细胞的基础上赋予功能优势。分子建模表明，TRAV 12 - 2的种系编码的互补决定区（CDR）1α环对A2/LLW结合有重要作用，而不是传统的显性依赖于体细胞重排的CDR 3环。抗原识别的这种种系成分可以解释对A2/LLW表位特异性的T细胞应答的异常高的前体频率、流行率和免疫优势。
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.
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影响因子：
4.4
作者：
Dietrich, PY;Le Gal, FA;Valmori, D
通讯作者：
Valmori, D
影响因子：
11.2
作者：
Hebeisen, Michael;Schmidt, Julien;Rufer, Nathalie
通讯作者：
Rufer, Nathalie
影响因子：
4.4
作者：
Derre, Laurent;Ferber, Mathias;Speiser, Daniel E.
通讯作者：
Speiser, Daniel E.
影响因子：
3
作者：
Pettersen, EF;Goddard, TD;Ferrin, TE
通讯作者：
Ferrin, TE
影响因子：
4.8
作者：
Cole, David K.;Yuan, Fang;Sewell, Andrew K.
通讯作者：
Sewell, Andrew K.