Identification of epitopes recognised by mucosal CD4(+) T-cell populations from cattle experimentally colonised with Escherichia coli O157:H7.
Identification of epitopes recognised by mucosal CD4(+) T-cell populations from cattle experimentally colonised with Escherichia coli O157:H7.
复制标题
DOI：
10.1186/s13567-016-0374-5
复制
发表时间：
2016-09-02
影响因子：
4.4
通讯作者：
McNeilly TN
中科院分区：
文献类型：
--
作者：
Corbishley A;Connelley TK;Wolfson EB;Ballingall K;Beckett AE;Gally DL;McNeilly TN
针对牛中肠出血性大肠杆菌（EHEC）O 157：H7散毒的疫苗仅具有部分保护作用。这些疫苗的保护相关性尚不清楚，但它们可能通过诱导阻断抗体减少粘膜表面的细菌粘附。最近的研究表明，细胞免疫在牛的殖民过程中的作用，提供了一个动力，以了解在这种反应过程中识别的细菌表位。本研究定位了产滋贺毒素EHEC O 157：H7菌株感染犊牛后直肠淋巴结CD 4 + T细胞识别的16种EHEC O 157：H7蛋白的表位。20个E.对其中7个蛋白质进行了鉴定。Intimin的高度保守的N-末端区域，包括信号肽，被来自不同主要组织相容性复合体II类单倍型的多个动物的粘膜CD 4 + T细胞群体一致地识别。这些T细胞表位在已发表的疫苗试验中使用的许多Intimin构建体中缺失，但在一系列EHEC血清型中相对保守，提供了开发交叉保护性疫苗的潜力。识别H7鞭毛蛋白的抗体一直在定殖小牛中鉴定;然而，在本研究中未鉴定来自H7鞭毛蛋白的CD 4 + T细胞表位，表明H7鞭毛蛋白可能作为T细胞非依赖性抗原。这是第一次在任何物种中表征了在用附着和消除病原体定殖后由CD 4 + T细胞识别的表位。这些发现对下一代EHEC O 157：H7疫苗中使用的抗原设计具有影响。本文的在线版本（doi：10.1186/s13567-016-0374-5）包含补充材料，可供授权用户使用。
Vaccines targeting enterohaemorrhagic Escherichia coli (EHEC) O157:H7 shedding in cattle are only partially protective. The correlates of protection of these vaccines are unknown, but it is probable that they reduce bacterial adherence at the mucosal surface via the induction of blocking antibodies. Recent studies have indicated a role for cellular immunity in cattle during colonisation, providing an impetus to understand the bacterial epitopes recognised during this response. This study mapped the epitopes of 16 EHEC O157:H7 proteins recognised by rectal lymph node CD4+ T-cells from calves colonised with Shiga toxin producing EHEC O157:H7 strains. 20 CD4+ T-cell epitopes specific to E. coli from 7 of the proteins were identified. The highly conserved N-terminal region of Intimin, including the signal peptide, was consistently recognised by mucosal CD4+ T-cell populations from multiple animals of different major histocompatibility complex class II haplotypes. These T-cell epitopes are missing from many Intimin constructs used in published vaccine trials, but are relatively conserved across a range of EHEC serotypes, offering the potential to develop cross protective vaccines. Antibodies recognising H7 flagellin have been consistently identified in colonised calves; however CD4+ T-cell epitopes from H7 flagellin were not identified in this study, suggesting that H7 flagellin may act as a T-cell independent antigen. This is the first time that the epitopes recognised by CD4+ T-cells following colonisation with an attaching and effacing pathogen have been characterised in any species. The findings have implications for the design of antigens used in the next generation of EHEC O157:H7 vaccines. The online version of this article (doi:10.1186/s13567-016-0374-5) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
3.1
作者：
Dean-Nystrom, EA;Gansheroff, LJ;O'Brien, AD
通讯作者：
O'Brien, AD
影响因子：
5.4
作者：
GLASS, EJ;SPOONER, RL
通讯作者：
SPOONER, RL
影响因子：
--
作者：
Asper, David J.;Karmali, Mohamed A.;Potter, Andrew A.
通讯作者：
Potter, Andrew A.
影响因子：
14.9
作者：
Simossis VA;Heringa J
通讯作者：
Heringa J
影响因子：
3.2
作者：
Ballingall, Keith T.;Tassi, Riccardo
通讯作者：
Tassi, Riccardo