Interaction of the hepatitis B core antigen and the innate immune system.
Interaction of the hepatitis B core antigen and the innate immune system.
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DOI：
10.4049/jimmunol.0803683
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发表时间：
2009-06-01
期刊：
影响因子：
--
通讯作者：
Milich DR
中科院分区：
文献类型：
--
作者：
Lee BO;Tucker A;Frelin L;Sallberg M;Jones J;Peters C;Hughes J;Whitacre D;Darsow B;Peterson DL;Milich DR
以往的研究表明，肝炎核心抗原(HBcAg)的主要抗原提呈细胞(APC)是B细胞，而不是树突状细胞(DC)。我们现在报告，与脾B2细胞相比，脾B1a和B1B细胞更有效地将可溶性HBcAg呈递给幼稚的CD4+T细胞。直接的HBcAg-生物素结合研究和体外培养的单纯HBcAg特异性T细胞和静止的B细胞亚群中HBcAg特异性T细胞的激活证明了这一点。DC不能作为外源性HBcAg的抗原前体与缺乏对HBcAg的摄取有关，而不是加工或提呈，因为DC可以有效地提呈HBcAg/抗HBc免疫复合物。此外，HBcAg特异性的CD4+和CD8+T细胞与编码HBcAg的DNA一起启动不需要B细胞APC。另一种先天免疫反应Toll样受体(TLR)的激活也被检测到。在表达人TLR的HEK293细胞中，筛选全长(HBcAg183)、截短型(HBcAg149)和非颗粒型HBeAg通过核因子-Kβ的激活来刺激TLR。HBC/HBeAgs均未激活人TLR。因此，HBC/HBeAg蛋白不是人TLRs的配体。然而，HBcAg183中包含的单链RNA确实作为TLR-7配体发挥作用，这在TLR-7基因敲除(KO)小鼠的T和B细胞水平上得到了证明。HBcAg183中的细菌、酵母和哺乳动物的单链RNA都是TLR-7的配体。这些研究表明，先天免疫机制连接并增强了对HBcAg的获得性免疫反应，并对使用肝病毒核心蛋白作为疫苗载体平台具有重要意义。
Previous studies demonstrated that the primary antigen presenting cells (APCs) for the hepatitis core antigen (HBcAg) were B cells and not dendritic cells (DC). We now report that splenic B1a and B1b cells more efficiently present soluble HBcAg to naïve CD4+ T cells than splenic B2 cells. This was demonstrated by direct HBcAg-biotin binding studies and by HBcAg-specific T cell activation in vitro in cultures of naïve HBcAg-specific T cells and resting B cell subpopulations. The inability of DCs to function as APCs for exogenous HBcAg relates to lack of uptake of HBcAg, not to processing or presentation because HBcAg/anti-HBc immune complexes can be efficiently presented by DCs. Furthermore, HBcAg-specific CD4+ and CD8+ T cell priming with DNA encoding HBcAg does not require B cell APCs. Toll-like-receptor (TLR) activation, another innate immune response, was also examined. Full-length (HBcAg183), truncated (HBcAg149) and the nonparticulate HBeAg were screened for TLR stimulation via NF-Kβ activation in HEK293 cells expressing human TLRs. None of the HBc/HBeAgs activated human TLRs. Therefore, the HBc/HBeAg proteins are not ligands for human TLRs. However, the ssRNA contained within HBcAg183 does function as a TLR-7 ligand as demonstrated at the T and B cell levels in TLR-7 knock-out (KO) mice. Bacterial, yeast and mammalian ssRNA encapsidated within HBcAg183 all function as TLR-7 ligands. These studies indicate that innate immune mechanisms bridge to and enhance the adaptive immune response to HBcAg and have important implications for the use of hepadnavirus core proteins as vaccine carrier platforms.
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影响因子：
5.5
作者：
Billaud, Jean-Noel;Peterson, Darrell;Milich, David
通讯作者：
Milich, David
影响因子：
64.8
作者：
Bottcher, B;Wynne, SA;Crowther, RA
通讯作者：
Crowther, RA
影响因子：
3.8
作者：
Lazdina, U;Alheim, M;Sällberg, M
通讯作者：
Sällberg, M
影响因子：
4.4
作者：
Cooper, A;Tal, G;Shaul, Y
通讯作者：
Shaul, Y
DOI：
10.1073/pnas.1834404100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Belnap, DM;Watts, NR;Steven, AC
通讯作者：
Steven, AC