Identification of CD4+ T cell epitopes in C. burnetii antigens targeted by antibody responses.
Identification of CD4+ T cell epitopes in C. burnetii antigens targeted by antibody responses.
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DOI：
10.1371/journal.pone.0017712
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发表时间：
2011-03-15
期刊：
影响因子：
3.7
通讯作者：
Peters B
中科院分区：
文献类型：
--
作者：
Chen C;Dow C;Wang P;Sidney J;Read A;Harmsen A;Samuel JE;Peters B
贝氏柯克斯体是一种专性细胞内革兰氏阴性细菌，可引起人类急性Q热和慢性感染。灭活的全细胞疫苗是有效的，但疫苗接种可导致严重的局部或全身不良反应。尽管T细胞应答被认为是疫苗衍生的保护性免疫的关键，但C.贝氏体疫苗接种尚未阐明。由于在具有超过2，000个ORF的基因组中定位CD 4+表位是资源密集型的，我们专注于已知被抗体应答靶向的7种抗原。基于与鼠MHC II类分子H-2 IAb结合的生物信息学预测，从这些抗原中选择117种候选肽。我们筛选了这些肽在I C期被产生IFN-γ的CD 4 + T细胞识别。贝氏体全细胞疫苗（PI-WCV）接种C57 BL/6小鼠，并鉴定了来自四种不同蛋白质的8个不同表位。鉴定的表位靶标占总疫苗接种诱导的产生IFN-γ的CD 4 + T细胞的8%。鉴于C.对贝氏体进行了筛选，这表明优先考虑抗体反应靶向的抗原是识别大型病原体中至少一个CD 4+靶点子集的有效策略。最后，我们检查了PI-WCV接种小鼠中CD 4 + T细胞和抗体应答之间的联系的性质。我们发现了表位特异性CD 4 + T细胞为抗体产生提供的帮助中令人惊讶的不均匀模式，其可以对表位来源抗原特异性以及非特异性。这表明PI-WCV接种小鼠中CD 4+应答靶点的完整图谱可能包括未产生抗体应答的抗原。
Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes acute Q fever and chronic infections in humans. A killed, whole cell vaccine is efficacious, but vaccination can result in severe local or systemic adverse reactions. Although T cell responses are considered pivotal for vaccine derived protective immunity, the epitope targets of CD4+ T cell responses in C. burnetii vaccination have not been elucidated. Since mapping CD4+ epitopes in a genome with over 2,000 ORFs is resource intensive, we focused on 7 antigens that were known to be targeted by antibody responses. 117 candidate peptides were selected from these antigens based on bioinformatics predictions of binding to the murine MHC class II molecule H-2 IAb. We screened these peptides for recognition by IFN-γ producing CD4+ T cell in phase I C. burnetii whole cell vaccine (PI-WCV) vaccinated C57BL/6 mice and identified 8 distinct epitopes from four different proteins. The identified epitope targets account for 8% of the total vaccination induced IFN-γ producing CD4+ T cells. Given that less than 0.4% of the antigens contained in C. burnetii were screened, this suggests that prioritizing antigens targeted by antibody responses is an efficient strategy to identify at least a subset of CD4+ targets in large pathogens. Finally, we examined the nature of linkage between CD4+ T cell and antibody responses in PI-WCV vaccinated mice. We found a surprisingly non-uniform pattern in the help provided by epitope specific CD4+ T cells for antibody production, which can be specific for the epitope source antigen as well as non-specific. This suggests that a complete map of CD4+ response targets in PI-WCV vaccinated mice will likely include antigens against which no antibody responses are made.
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影响因子：
4.4
作者：
Arens, Ramon;Wang, Peng;Benedict, Chris A.
通讯作者：
Benedict, Chris A.
DOI：
10.1111/j.1749-6632.1990.tb42263.x
发表时间：
1990-06-26
影响因子：
5.2
作者：
HENDRIX, LR;SAMUEL, JE;MALLAVIA, LP
通讯作者：
MALLAVIA, LP
影响因子：
--
作者：
Beare, Paul A.;Chen, Chen;Heinzen, Robert A.
通讯作者：
Heinzen, Robert A.
DOI：
10.1073/pnas.0409880102
发表时间：
2005-02-22
影响因子：
11.1
作者：
Bynoe, MS;Viret, C;Janeway, CA
通讯作者：
Janeway, CA
DOI：
10.4049/jimmunol.181.7.4955
发表时间：
2008-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Forbes EK;Sander C;Ronan EO;McShane H;Hill AV;Beverley PC;Tchilian EZ
通讯作者：
Tchilian EZ