Effect of MHC class I diversification on influenza epitope-specific CD8+ T cell precursor frequency and subsequent effector function.
Effect of MHC class I diversification on influenza epitope-specific CD8+ T cell precursor frequency and subsequent effector function.
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DOI：
10.4049/jimmunol.1000883
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Turner SJ
中科院分区：
文献类型：
--
作者：
Day EB;Charlton KL;La Gruta NL;Doherty PC;Turner SJ
流感特异性CD8+ T细胞免疫优势等级的早期研究表明，H2Kk MHCI等位基因的表达大大降低了对H2Db限制性DbPA224表位的应答。结果表明，胸腺分化期间H2Kk的存在导致DbPA 224特异性TCR的显著Vβ7+亚群的缺失。在H2b小鼠中DbPA 224特异性TCR CDR3β库的最新定义为再次观察这种可能的H2Kk对DbPA 224特异性TCR选择的影响提供了新的基线。我们发现，与纯合子小鼠相比，H2bxk F1小鼠对几种H2Db和H2Kb限制性流感表位的免疫应答确实减少。在DbPA 224的情况下，幼稚前体的数量较低是部分解释，尽管DbNP 366表位特异性的类似减少并不影响响应幅度。前体频率的变化与TCR多样性的任何重大损失无关，并且不能完全解释DbPA 224特异性应答的减少。流感特异性CD8+ T细胞的进一步功能和表型表征表明，DbPA 224特异性集的扩增和分化在H2bxk F1环境中受损。因此，H2bxk F1小鼠中的DbPA 224应答受到影响初始表位特异性前体产生以及感染期间这些T细胞扩增和分化的因素的调节，而不是显著Vβ7+亚群的克隆缺失。这些发现说明了预测和定义MHCI多样化对表位特异性反应的影响的困难。
Earlier studies of influenza-specific CD8+ T cell immunodominance hierarchies indicated that expression of the H2Kk MHCI allele greatly diminishes responses to the H2Db-restriced DbPA224 epitope. The results suggested that the presence of H2Kk during thymic differentiation led to the deletion of a prominent Vβ7+ subset of DbPA224-specific TCRs. The more recent definition of DbPA224-specific TCR CDR3β repertoires in H2b mice provides a new baseline for looking again at this possible H2Kk effect on DbPA224-specific TCR selection. We found that immune responses to several H2Db- and H2Kb-restricted influenza epitopes were indeed diminished in H2bxk F1 versus homozygous mice. In the case of DbPA224, lower numbers of naïve precursors were part of the explanation, though a similar decrease in those specific for the DbNP366 epitope did not affect response magnitude. Changes in precursor frequency were not associated with any major loss of TCR diversity and could not fully account for the diminished DbPA224-specific response. Further functional and phenotypic characterisation of influenza-specific CD8+ T cells suggested that the expansion and differentiation of the DbPA224-specific set is impaired in the H2bxk F1 environment. Thus, the DbPA224 response in H2bxk F1 mice is modulated by factors that affect the generation of naïve epitope-specific precursors and the expansion and differentiation of these T cells during infection, rather than clonal deletion of a prominent Vβ7+ subset. Such findings illustrate the difficulties of predicting and defining the effects of MHCI diversification on epitope-specific responses.
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影响因子：
32.4
作者：
Correia-Neves, M;Waltzinger, C;Benoist, C
通讯作者：
Benoist, C
影响因子：
15.3
作者：
BURROWS, SR;SILINS, SL;ARGAET, VP
通讯作者：
ARGAET, VP
影响因子：
4.4
作者：
Ely, KH;Cauley, LS;Woodland, DL
通讯作者：
Woodland, DL
DOI：
10.4049/jimmunol.0900999
发表时间：
2010-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Flesch IE;Woo WP;Wang Y;Panchanathan V;Wong YC;La Gruta NL;Cukalac T;Tscharke DC
通讯作者：
Tscharke DC
影响因子：
32.4
作者：
Gras, Stephanie;Burrows, Scott R.;Rossjohn, Jamie
通讯作者：
Rossjohn, Jamie