TLR ligands differentially affect uptake and presentation of cellular antigens

TLR ligands differentially affect uptake and presentation of cellular antigens
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DOI:
10.1182/blood-2006-04-015719
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发表时间:
2007-05-01
期刊:
影响因子:
20.3
通讯作者:
Brossart, Peter
Brossart, Peter
中科院分区:
医学1区
文献类型:
--
作者:
Weck, Markus Michael;Gruenebach, Frank;Brossart, Peter

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树突状细胞 (DC) 具有独特的能力,可以有效地将外源抗原的 T 细胞表位呈递到 MHC I 类分子上,这一过程称为交叉呈递。在我们的研究中,我们证明用 Toll 样受体 (TLR) 配体刺激单核细胞衍生的 DC 会不同程度地影响细胞抗原的摄取和交叉呈递。用TLR3或TLR4而不是TLR2或TLR7/8配体激活DC会抑制凋亡肿瘤细胞的吞噬作用,并导致吞噬巨细胞病毒(CMV)感染的成纤维细胞后,MHC I类分子上pp65衍生的T细胞表位的交叉呈递减少。这些结果对于理解免疫系统与病原体之间的相互作用以及制定治疗恶性疾病的疫苗接种策略具有重要影响。
Dendritic cells (DCs) have the unique ability to efficiently present T-cell epitopes from exogenous antigens on MHC class I molecules, a process called cross-presentation. In our study we demonstrate that stimulation of monocyte-derived DCs with Toll-like receptor (TLR) ligands differentially affects the uptake and cross-presentation of cellular antigens. Activation of DCs with TLR3 or TLR4 but not with TLR2 or TLR7/8 ligands inhibited phagocytosis of apoptotic tumor cells and resulted in a reduced cross-presentation of pp65-derived T-cell epitopes on MHC class I molecules upon engulfment of cytomegalovirus (CMV)-infected fibroblasts. These results have an important impact on the understanding of the interactions between the immune system and pathogens and the development of vaccination strategies to treat malignant diseases.