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Modulation of immunoproteasome subunits by liposomal lipid A.

机译:脂质体脂质A对免疫蛋白酶体亚基的调节。

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摘要

Liposomes are phospholipid vesicles that have been used as carriers of antigens and adjuvants. Lipid A, the endotoxic moiety of Gram-negative bacterial lipopolysaccharide is a potent adjuvant and incorporation into liposomes essentially reduces the endotoxic activity of lipid A. In this study, we analyzed the effect of liposomal lipid A [L(LA)] on the MHC class I antigen processing machinery in murine antigen presenting cells (APCs). L(LA) enhanced the surface expression of MHC class I, class II, CD80, and CD86 molecules, induced the secretion of IFN-gamma, IL-12p40, TNF-alpha and IL-10, and caused a shift in the proteasome profile from constitutive to immunoproteasomes as observed by the induction of beta2i, beta5i, PA28alpha, and PA28beta subunits. L(LA) acts through the production of IFN-gamma as demonstrated with APCs generated from IFN-gamma knockout mice. L(LA) therefore appears to act as an intracellular adjuvant by upregulating the antigen processing machinery, which could result in efficient antigen presentation.
机译:脂质体是已被用作抗原和佐剂载体的磷脂囊泡。脂质A(革兰氏阴性细菌脂多糖的内毒素部分)是有效的佐剂,掺入脂质体中实质上降低了脂质A的内毒素活性。在这项研究中,我们分析了脂质体脂质A [L(LA)]对MHC的影响鼠抗原呈递细胞(APC)中的I类抗原加工机制。 L(LA)增强MHC I类,II类,CD80和CD86分子的表面表达,诱导IFN-γ,IL-12p40,TNF-α和IL-10的分泌,并引起蛋白酶体谱的改变β2i,beta5i,PA28alpha和PA28bet​​a亚基的诱导观察到从组成型到免疫蛋白酶体的转变。 L(LA)通过产生IFN-γ发挥作用,正如从IFN-γ敲除小鼠产生的APC所证明的。因此,L(LA)似乎通过上调抗原加工机制而充当细胞内佐剂,这可能导致有效的抗原呈递。

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