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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Bacterial Heat Shock Proteins Promote CD91-Dependent Class I MHC Cross-Presentation of Chaperoned Peptide to CD8~+ T Cells by Cytosolic Mechanisms in Dendritic Cells versus Vacuolar Mechanisms in Macrophages
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Bacterial Heat Shock Proteins Promote CD91-Dependent Class I MHC Cross-Presentation of Chaperoned Peptide to CD8~+ T Cells by Cytosolic Mechanisms in Dendritic Cells versus Vacuolar Mechanisms in Macrophages

机译:细菌热激蛋白通过树突状细胞中的胞质机制与巨噬细胞中的液泡机制促进CD91依赖的I类MHC伴侣蛋白向CD8〜+ T细胞的交叉表达。

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摘要

APCs process mammalian heat shock protein (HSP):peptide complexes to present HSP-chaperoned peptides on class I MHC (MHC-I) molecules to CD8~+ T cells. HSPs are also expressed in prokaryotes and chaperone microbial peptides, but the ability of prokaryotic HSPs to contribute chaperoned peptides for Ag presentation is unknown. Our studies revealed that exogenous bacterial HSPs (Escherichia coli DnaK and Mycobacterium tuberculosis HSP70) delivered an extended OVA peptide for processing and MHC-I presentation by both murine macrophages and dendritic cells. HSP-enhanced MHC-I peptide presentation occurred only if peptide was complexed to the prokaryotic HSP and was dependent on CD91, establishing CD91 as a receptor for prokaryotic as well as mammalian HSPs. Inhibition of cytosolic processing mechanisms (e.g., by transporter for Ag presentation deficiency or brefeldin A) blocked HSP-enhanced peptide presentation in dendritic cells but not macrophages. Thus, prokaryotic HSPs deliver chaperoned peptide for alternate MHC-I Ag processing and cross-presentation via cytosolic mechanisms in dendritic cells and vacuolar mechanisms in macrophages. Prokaryotic HSPs are a potential source of microbial peptide Ags during phago-cytic processing of bacteria during infection and could potentially be incorporated in vaccines to enhance presentation of peptides to CD8~+ T cells.
机译:APC处理哺乳动物热休克蛋白(HSP):肽复合物,将I类MHC(MHC-1)分子上的HSP伴侣肽呈递给CD8〜+ T细胞。 HSPs在原核生物和伴侣蛋白微生物肽中也有表达,但是原核HSPs贡献伴侣蛋白肽用于Ag呈递的能力尚不清楚。我们的研究表明,外源细菌HSP(大肠杆菌DnaK和结核分枝杆菌HSP70)提供了扩展的OVA肽,可用于鼠巨噬细胞和树突状细胞的加工和MHC-1呈递。仅当肽复合到原核HSP且依赖于CD91时,HSP增强的MHC-1肽才会出现,从而将CD91建立为原核以及哺乳动物HSP的受体。抑制胞质加工机制(例如通过转运蛋白表达缺陷或布雷菲德菌素A)可阻止树突状细胞中HSP增强的肽表达,但不能阻止巨噬细胞。因此,原核HSPs通过树突状细胞中的胞质机制和巨噬细胞中的液泡机制,为伴随的MHC-1 Ag加工和交叉呈递提供了伴侣蛋白。原核热休克蛋白是细菌吞噬过程中感染过程中微生物肽Ags的潜在来源,并有可能被掺入疫苗中以增强肽向CD8 + T细胞的呈递。

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