Altered CD8(+) T cell immunodominance after vaccinia virus infection and the naive repertoire in inbred and F(1) mice.
Altered CD8(+) T cell immunodominance after vaccinia virus infection and the naive repertoire in inbred and F(1) mice.
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DOI：
10.4049/jimmunol.0900999
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Tscharke DC
中科院分区：
文献类型：
--
作者：
Flesch IE;Woo WP;Wang Y;Panchanathan V;Wong YC;La Gruta NL;Cukalac T;Tscharke DC
先前的研究表明，与其近交系亲本相比，F1小鼠初次病毒感染后的CD8 + T细胞免疫优势没有发生显着变化。在这里，我们使用牛痘病毒（VACV）重新访问这个问题，它具有大的基因组，最近定义的小鼠免疫优势等级，是疫苗的候选载体。我们发现，使用近交系小鼠定义的VACV肽的免疫原性在F1子代中是高度可变的：一些肽在F1和近交系中具有相同的免疫原性，而另一些肽引起的反应在F1小鼠中减少了90%以上。此外，肽在相关近交亲本中的优势并不能预测它在F1小鼠中是否具有不良免疫原性。这一结果适用于MHC同源小鼠的F1杂交，表明MHC差异单独负责。它还扩展到由重组VACV疫苗表达的外源表位。当用作唯一免疫原时，F1小鼠不太能够对免疫原性差的肽产生应答，排除了免疫优势。此外，近交系和F1小鼠之间保守的TCR V β使用并不总是与F1小鼠中的强反应相关。然而，对幼稚前体数量的直接估计表明，与近交系小鼠相比，F1中的幼稚前体数量有所减少，因为杂交种的免疫原性较差。这些数据对我们理解MHC多样性在多大程度上改变远系繁殖群体中免疫原性表位的范围具有影响。
Previous studies of CD8+ T cell immunodominance after primary virus infection of F1 mice compared with their inbred parents have generally concluded that no dramatic changes occur. Here we re-visit this issue using vaccinia virus (VACV), which has a large genome, a recently defined immunodominance hierarchy in mice and is a candidate vector for vaccines. We found that immunogenicity of VACV peptides defined using inbred mice was highly variable in F1 progeny: some peptides were equally immunogenic in F1 and inbred, while others elicited responses that were reduced by more than 90% in F1 mice. Further, the dominance of a peptide in the relevant inbred parent did not predict whether or not it would be poorly immunogenic in F1 mice. This result held using F1 hybrids of MHC-congenic mice, suggesting that MHC differences alone were responsible. It was also extended to foreign epitopes expressed by a recombinant VACV vaccine. F1 mice were less able to mount responses to the poorly immunogenic peptides when used as a sole immunogen, ruling out immunodomination. In addition, conserved TCR Vβ usage between inbred and F1 mice did not always correlate with strong responses in F1 mice. However direct estimation of naïve precursor numbers showed that these were reduced in F1 compared with inbred mice for specificities that were poorly immunogenic in the hybrids. These data have implications for our understanding of the extent to which MHC diversity alters the range of epitopes that are immunogenic in outbred populations.
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原代T细胞反应的组成在很大程度上取决于单个T细胞克隆的募集时间。
DOI：
10.1084/jem.189.10.1591
发表时间：
1999-05-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bousso P;Levraud JP;Kourilsky P;Abastado JP
通讯作者：
Abastado JP
影响因子：
5.4
作者：
Andreansky, SS;Stambas, J;Doherty, PC
通讯作者：
Doherty, PC
影响因子：
15.3
作者：
BURROWS, SR;SILINS, SL;ARGAET, VP
通讯作者：
ARGAET, VP
影响因子：
168.9
作者：
Greenberg, RN;Kennedy, JS;Hopkins, RJ
通讯作者：
Hopkins, RJ
影响因子：
4.4
作者：
Haeryfar, SMM;DiPaolo, RJ;Yewdell, JW
通讯作者：
Yewdell, JW