Listeriolysin o is strongly immunogenic independently of its cytotoxic activity.
Listeriolysin o is strongly immunogenic independently of its cytotoxic activity.
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DOI：
10.1371/journal.pone.0032310
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Unanue ER
中科院分区：
文献类型：
--
作者：
Carrero JA;Vivanco-Cid H;Unanue ER
主要组织相容性复合物（MHC）分子对微生物蛋白抗原的呈递对于感染获得性免疫的发展至关重要。然而，大多数抗原加工和呈递的生物化学研究涉及一些相对惰性的非微生物模型抗原。细菌成孔毒素溶血素O（LLO）是矛盾的，因为它在纳摩尔浓度下具有细胞毒性，并且是单核细胞增生李斯特菌感染后显性CD 4和CD 8 T细胞表位的来源。在这里，我们研究了LLO毒性与其抗原性和免疫原性的关系。LLO作为可溶性蛋白质提供给抗原递呈细胞（APC），以皮摩尔至飞摩尔浓度递呈给CD 4 T细胞-剂量比游离肽低3000-7000倍。这种情况需要低于细胞毒性水平的LLO剂量。两个关键色氨酸残基的突变使LLO毒性降低10-100倍，但对其向CD 4 T细胞的呈递没有影响。因此，LLO的细胞毒性特性与其非常高的抗原性之间存在明显的分离。LLO向CD 8 T细胞的呈递不像在CD 4 T细胞中所见的那样稳健，但仍在纳摩尔范围内发生。APC快速结合并内化LLO，然后在处理的4小时内破坏内体区室，允许内体内容物进入胞质溶胶。LLO在体内给药至小鼠后也具有免疫原性。我们的结果证明了LLO作为CD 4和CD 8 T细胞的免疫原的强度。
The presentation of microbial protein antigens by Major Histocompatibility Complex (MHC) molecules is essential for the development of acquired immunity to infections. However, most biochemical studies of antigen processing and presentation deal with a few relatively inert non-microbial model antigens. The bacterial pore-forming toxin listeriolysin O (LLO) is paradoxical in that it is cytotoxic at nanomolar concentrations as well as being the source of dominant CD4 and CD8 T cell epitopes following infection with Listeria monocytogenes. Here, we examined the relationship of LLO toxicity to its antigenicity and immunogenicity. LLO offered to antigen presenting cells (APC) as a soluble protein, was presented to CD4 T cells at picomolar to femtomolar concentrations- doses 3000–7000-fold lower than free peptide. This presentation required a dose of LLO below the cytotoxic level. Mutations of two key tryptophan residues reduced LLO toxicity by 10–100-fold but had no effect on its presentation to CD4 T cells. Thus there was a clear dissociation between the cytotoxic properties of LLO and its very high antigenicity. Presentation of LLO to CD8 T cells was not as robust as that seen in CD4 T cells, but still occurred in the nanomolar range. APC rapidly bound and internalized LLO, then disrupted endosomal compartments within 4 hours of treatment, allowing endosomal contents to access the cytosol. LLO was also immunogenic after in vivo administration into mice. Our results demonstrate the strength of LLO as an immunogen to both CD4 and CD8 T cells.
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DOI：
10.1083/jcb.200201081
发表时间：
2002-03-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Glomski IJ;Gedde MM;Tsang AW;Swanson JA;Portnoy DA
通讯作者：
Portnoy DA
影响因子：
4.1
作者：
GREENWOOD, FC;HUNTER, WM
通讯作者：
HUNTER, WM
影响因子：
3.1
作者：
GAILLARD, JL;BERCHE, P;SANSONETTI, P
通讯作者：
SANSONETTI, P
影响因子：
32.4
作者：
Edelson, BT;Unanue, ER
通讯作者：
Unanue, ER
影响因子：
3.1
作者：
Barsig, J;Kaufmann, SHE
通讯作者：
Kaufmann, SHE