Cross-competition of CD8+ T cells shapes the immunodominance hierarchy during boost vaccination.
Cross-competition of CD8+ T cells shapes the immunodominance hierarchy during boost vaccination.
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DOI：
10.1084/jem.20070489
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发表时间：
2007-09-03
期刊：
影响因子：
--
通讯作者：
Drexler I
中科院分区：
文献类型：
--
作者：
Kastenmuller W;Gasteiger G;Gronau JH;Baier R;Ljapoci R;Busch DH;Drexler I
针对多个病原体衍生表位的 CD8+ T 细胞反应以明确的免疫优势层次模式为特征。对于这种现象的一个可能的解释是，不同特异性的 CD8+ T 细胞竞争接近抗原呈递细胞上的表位，这种所谓的交叉竞争的结果反映了诱导 T 细胞的数量。在我们使用牛痘病毒感染模型的研究中，我们发现 T 细胞交叉竞争在加强疫苗接种过程中高度相关，从而塑造了召回中的免疫优势等级。我们证明竞争在启动期间并不重要，并且不受所应用的免疫途径的影响。它在很大程度上取决于受感染的 APC 中病毒抗原表达的时间，其特点是识别源自晚期病毒蛋白的表位的 T 细胞增殖不良。据我们所知，这是病毒感染期间 T 细胞交叉竞争的功能重要性的首次证明。我们的研究结果为如何选择性地改进特定抗原的加强疫苗接种的新策略提供了基础。他们为设计用于免疫治疗的更有效的痘病毒载体提供了重要的新见解。
CD8+ T cell responses directed against multiple pathogen-derived epitopes are characterized by defined immunodominance hierarchy patterns. A possible explanation for this phenomenon is that CD8+ T cells of different specificities compete for access to epitopes on antigen-presenting cells, and that the outcome of this so-called cross-competition reflects the number of induced T cells. In our study using a vaccinia virus infection model, we found that T cell cross-competition is highly relevant during boost vaccination, thereby shaping the immunodominance hierarchy in the recall. We demonstrate that competition was of no importance during priming and was unaffected by the applied route of immunization. It strongly depended on the timing of viral antigen expression in infected APCs, and it was characterized by poor proliferation of T cells recognizing epitopes derived from late viral proteins. To our knowledge, this is the first demonstration of the functional importance of T cell cross-competition during a viral infection. Our findings provide a basis for novel strategies for how boost vaccination to defined antigens can be selectively improved. They give important new insights into the design of more efficient poxviral vectors for immunotherapy.
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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：
4.4
作者：
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通讯作者：
Yewdell, JW
DOI：
10.1073/pnas.0609990104
发表时间：
2007-04-10
影响因子：
11.1
作者：
Belz, Gabrielle T.;Zhang, Lei;Davenport, Miles P.
通讯作者：
Davenport, Miles P.
影响因子：
4.4
作者：
Pasquetto, V;Bui, HH;Sette, A
通讯作者：
Sette, A
影响因子：
4.4
作者：
Jenkins, Misty Rayna;Webby, Richard;Turner, Stephen J.
通讯作者：
Turner, Stephen J.