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CpG-DNA通过交叉呈递B细胞辅助交叉启动。

CpG-DNA aided cross-priming by cross-presenting B cells.

作者信息

Heit Antje, Huster Katharina M, Schmitz Frank, Schiemann Matthias, Busch Dirk H, Wagner Hermann

机构信息

Institute of Medical Microbiology, Immunology and Hygiene, Technical University Munich, Munich, Germany.

出版信息

J Immunol. 2004 Feb 1;172(3):1501-7. doi: 10.4049/jimmunol.172.3.1501.

Abstract

Covalent linkage of immunostimulatory CpG-DNA to OVA (CpG-OVA complex) results in CpG-DNA-aided cross-presentation of OVA by dendritic cells (DCs). In this study, we analyzed the thesis that CpG-OVA complexes may be cross-presented by B cells to route internalized Ag into the class I MHC presentation pathway. First, we describe that conjugation of CpG-DNA to OVA enhances up to 40-fold internalization of OVA by B cells, which in turn generate the CD8 T cell epitope SIINFEKL complexed to MHC class I, albeit less efficiently than DCs. Furthermore, upon internalization, CpG-DNA conjugated to OVA stimulates B cells to up-regulate costimulatory molecules and cytokines including IL-12. Adoptive transfer of CpG-OVA complex-loaded wild-type B cells cross-primes naive CD8 T cells both in wild-type mice and in MyD88-deficient mice. Overall, these findings disclose attributes of B cells, including cross-presentation of exogenous Ag and cross-priming of naive CD8 T cells that hitherto have been considered as hallmarks restricted to DCs.

摘要

免疫刺激型CpG-DNA与卵清蛋白(OVA)的共价连接(CpG-OVA复合物)导致CpG-DNA辅助树突状细胞(DCs)对OVA进行交叉呈递。在本研究中,我们分析了CpG-OVA复合物可能由B细胞进行交叉呈递,从而将内化的抗原导入I类主要组织相容性复合体(MHC)呈递途径这一论点。首先,我们描述了CpG-DNA与OVA的结合使B细胞对OVA的内化增强了40倍,这反过来又产生了与I类MHC复合的CD8 T细胞表位SIINFEKL,尽管效率低于DCs。此外,内化后,与OVA结合的CpG-DNA刺激B细胞上调共刺激分子和包括白细胞介素-12在内的细胞因子。在野生型小鼠和MyD88缺陷型小鼠中,过继转移负载CpG-OVA复合物的野生型B细胞均可交叉启动初始CD8 T细胞。总体而言,这些发现揭示了B细胞的特性,包括对外源抗原的交叉呈递和对初始CD8 T细胞的交叉启动,而这些特性迄今为止一直被认为是DCs所特有的标志。

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