CD8+ T cells specific for a single nonamer epitope of Listeria monocytogenes are protective in vivo.

CD8+ T cells specific for a single nonamer epitope of Listeria monocytogenes are protective in vivo.
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DOI:
10.1084/jem.175.6.1531
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发表时间:
1992-06-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Bevan MJ
Bevan MJ
中科院分区:
其他
文献类型:
--
作者:
Harty JT;Bevan MJ

文献摘要

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I类主要组织相容性复合体(MHC)限制性CD8 + T细胞已被证明是对细胞内细菌单核细胞增生李斯特菌的获得性和过继性免疫的有效介质。我们最近确定L.单核细胞增多症感染的H-2d小鼠以H-2Kd-限制的方式识别分泌的蛋白溶血素O(LLO)的九聚体肽,残基91 - 99。在本报告中,我们通过用LLO转染的P815(H-2d)细胞体外刺激,在H-2Kd的背景下产生了对LLO 91 - 99具有特异性的CD8 + T细胞系。这些CD8+细胞系是由免疫供体亚致死感染L.单核细胞增多症,或在用合成LLO 91 - 99肽包被的同基因脾细胞体内免疫后。来自任一方案的LLO特异性CD8 + T细胞能够显著保护免受L.单核细胞增生感染。这些CD 8 + T细胞系的体内保护作用已被证明完全是由于在H-2 Kd的背景下识别LLO 91 - 99。这些研究表明,CD8 + T细胞对单个天然产生的肽表位的免疫具有在细菌感染中显著保护的潜力。因此,等位基因特异性基序的表位预测方法已经确定了一个天然产生的细菌表位与生物学相关性。
Class I major histocompatibility complex (MHC)-restricted CD8+ T cells have been demonstrated to be effective mediators of both acquired and adoptive immunity to the intracellular bacterium Listeria monocytogenes. We have recently determined that L. monocytogenes- infected H-2d mice recognize a nonamer peptide, residues 91-99, of the secreted protein listeriolysin O (LLO), in a H-2Kd-restricted fashion. In this report we have generated CD8+ T cell lines with specificity for LLO 91-99 in the context of H-2Kd by in vitro stimulation with P815 (H- 2d) cells transfected with LLO. These CD8+ lines have been generated from immune donors after sublethal infection with L. monocytogenes, or after in vivo immunization with syngeneic spleen cells coated with synthetic LLO 91-99 peptide. LLO-specific CD8+ T cells derived from either protocol were capable of significant protection against L. monocytogenes infection. The in vivo protection by these CD8+ T cell lines has been shown to be solely due to recognition of LLO 91-99 in the context of H-2Kd. These studies demonstrate that CD8+ T cell immunity to a single, naturally produced peptide epitope has the potential for significant protection in a bacterial infection. Thus, the allele-specific motif approach to epitope prediction has identified a naturally produced bacterial epitope with biological relevance.