H2-M3-restricted CD8+ T cells are not required for MHC class Ib-restricted immunity against Listeria monocytogenes.

H2-M3-restricted CD8+ T cells are not required for MHC class Ib-restricted immunity against Listeria monocytogenes.
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DOI:
10.1084/jem.20052256
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发表时间:
2006-02-20
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Starnbach MN
Starnbach MN
中科院分区:
其他
文献类型:
--
作者:
D'Orazio SE;Shaw CA;Starnbach MN

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对主要组织相容性复合体(MHC)- ia缺陷小鼠的研究表明,MHC- ib限制性CD8+ T细胞可以清除细胞内病原体(如单核增生李斯特菌)引起的感染。m3限制性CD8+ T细胞识别短疏水性n -甲酰化肽,似乎在单核增生乳杆菌感染小鼠模型中构成了mhc - b限制性T细胞反应的很大一部分。在这项研究中,我们分离了缺乏向新生多肽添加甲酰基能力的单核增生乳杆菌的甲酰基转移酶(fmt)突变菌株。这些fmt突变李斯特菌株不产生可被m3限制性T细胞识别的抗原。我们发现mhc - ia缺陷小鼠与fmt突变李斯特菌免疫导致保护性记忆反应的刺激,清除随后的野生型单核增生乳杆菌的攻击,尽管事实上m3限制性CD8+ T细胞在这些小鼠中没有增殖。这些数据表明,m3限制性T细胞对单核增生乳杆菌的保护并不需要,并强调了在大型MHC-Ib蛋白家族中寻找新的抗原呈递分子的重要性。
Studies using major histocompatibility complex (MHC)-Ia–deficient mice have shown that MHC-Ib–restricted CD8+ T cells can clear infections caused by intracellular pathogens such as Listeria monocytogenes. M3-restricted CD8+ T cells, which recognize short hydrophobic N-formylated peptides, appear to comprise a substantial portion of the MHC-Ib–restricted T cell response in the mouse model of L. monocytogenes infection. In this study, we isolated formyltransferase (fmt) mutant strains of L. monocytogenes that lacked the ability to add formyl groups to nascent polypeptides. These fmt mutant Listeria strains did not produce antigens that could be recognized by M3-restricted T cells. We showed that immunization of MHC-Ia–deficient mice with fmt mutant Listeria resulted in stimulation of a protective memory response that cleared subsequent challenge with wild-type L. monocytogenes, despite the fact that M3-restricted CD8+ T cells did not proliferate in these mice. These data suggest that M3-restricted T cells are not required for protection against L. monocytogenes and underscore the importance of searching for new antigen-presenting molecules among the large MHC-Ib family of proteins.
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