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Simultaneous cognate epitope recognition by bovine CD4 and CD8 T cells is essential for primary expansion of antigen-specific cytotoxic T-cells following ex vivo stimulation with a candidate Mycobacterium avium subsp. paratuberculosis peptide vaccine.
Vaccine ( IF 5.5 ) Pub Date : 2020-01-03 , DOI: 10.1016/j.vaccine.2019.12.052
Gaber S Abdellrazeq 1 , Lindsay M Fry 2 , Mahmoud M Elnaggar 1 , John P Bannantine 3 , David A Schneider 2 , William M Chamberlin , Asmaa H A Mahmoud 4 , Kun-Taek Park 5 , Victoria Hulubei 6 , William C Davis 6
Affiliation  

Studies in cattle show CD8 cytotoxic T cells (CTL), with the ability to kill intracellular bacteria, develop following stimulation of monocyte-depleted peripheral blood mononuclear cells (mdPBMC) with antigen presenting cells (APC, i.e. conventional dendritic cells [cDC] and monocyte-derived DC [MoDC]) pulsed with MMP, a membrane protein from Mycobacterium avium subsp. paratuberculosis (Map) encoded by MAP2121c. CTL activity was diminished if CD4 T cells were depleted from mdPBMC before antigen (Ag) presentation by APC, suggesting simultaneous cognate recognition of MMP epitopes presented by MHC I and MHC II molecules to CD4 and CD8 T cells is essential for development of CTL activity. To explore this possibility, studies were conducted with mdPBMC cultures in the presence of monoclonal antibodies (mAbs) specific for MHC class I and MHC class II molecules. The CTL response of mdPBMC to MMP-pulsed APC was completely blocked in the presence of mAbs to both MHC I and II molecules and also blocked in the presence of mAbs to either MHC I or MHC II alone. The results demonstrate simultaneous cognate recognition of Ag by CD4 and CD8 T cells is essential for delivery of CD4 T cell help to CD8 T cells to elicit development of CTL.

中文翻译:

牛CD4和CD8 T细胞同时识别同源表位对于在候选鸟分枝杆菌亚种离体刺激后抗原特异性细胞毒性T细胞的初步扩增至关重要。副肺结核肽疫苗。

牛的研究表明,具有抗原杀伤性抗原呈递细胞(APC,即常规树突状细胞[cDC]和单核细胞)刺激单核细胞耗竭的外周血单核细胞(mdPBMC)后,具有杀死细胞内细菌能力的CD8细胞毒性T细胞(CTL) MMP(鸟分枝杆菌亚种的膜蛋白)脉冲处理的来源DC(MoDC))。MAP2121c编码的副结核病(Map)。如果在APC抗原(Ag)呈递之前从mdPBMC中耗尽了CD4 T细胞,CTL活性就会降低,这表明MHC I和MHC II分子同时向CD4和CD8 T细胞呈递的MMP表位的同源识别对于CTL活性的发展至关重要。为了探索这种可能性,在存在针对I类MHC和II类MHC分子的单克隆抗体(mAb)的情况下,使用mdPBMC培养进行了研究。在存在针对MHC I和II分子的单克隆抗体的情况下,mdPBMC对MMP脉冲APC的CTL响应被完全阻断,并且在存在针对MHC I或MHC II的单克隆抗体的情况下也被完全阻断。结果表明,CD4和CD8 T细胞对Ag的同时同源识别对于将CD4 T细胞帮助递送至CD8 T细胞以引发CTL的发育至关重要。
更新日期:2020-01-04
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