CD91-dependent programming of T-helper cell responses following heat shock protein immunization.

CD91-dependent programming of T-helper cell responses following heat shock protein immunization.
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DOI:
10.1038/ncomms1524
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发表时间:
2011-11-01
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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免疫原性热休克蛋白(HSP)gp 96、hsp 70和钙网蛋白与抗原呈递细胞上的CD 91结合以交叉呈递HSP陪伴的肽。该事件导致T细胞应答的引发。我们表明,CD 91作为这些热休克蛋白的信号受体,允许成熟的抗原呈递细胞(APC),分泌细胞因子,并引发T辅助细胞。具体而言,CD 91以独特的模式响应于HSP而磷酸化,并且磷酸化-CD 91触发信号传导级联以激活NF-κB。抗原呈递细胞上的每个HSP-CD 91相互作用刺激独特的细胞因子谱,其指示特异性T辅助细胞亚群的引发。因此,在TGF-β肿瘤微环境中,用钙网蛋白而不是gp 96或hsp 70免疫以CD 91依赖性方式引发Th 17细胞应答。这些结果对于肿瘤宿主原位T细胞反应的发展以及针对癌症和传染病的疫苗接种是重要的。
The immunogenic Heat shock proteins (HSPs) gp96, hsp70 and calreticulin bind to CD91 on antigen presenting cells for cross-presentation of the HSP-chaperoned peptides. This event leads to priming of T cell responses. We show that CD91 serves as a signaling receptor for these HSPs allowing for the maturation of the antigen presenting cells (APC), secretion of cytokines, and priming of T helper cells. Specifically, CD91 is phosphorylated in response to HSPs in a unique pattern and phospho-CD91 triggers signaling cascades to activate NF-κB. Each HSP-CD91 interaction on antigen presenting cells stimulates a unique cytokine profile which dictates priming of specific T helper cell subsets. Thus, in a TGF-β tumor microenvironment, immunization with calreticulin but not gp96 or hsp70 primes Th17 cell responses in a CD91-dependent manner. These results are important for development of T cell responses in situ in tumor-bearing hosts and for vaccination against cancer and infectious disease.
DOI: 10.1038/nature04753
发表时间: 2006-05-11
期刊: NATURE
影响因子: 64.8
作者:
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者: Kuchroo, VK
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发表时间: 2001-04-15
影响因子: 4.4
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发表时间: 2002-04-26
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发表时间: 1999-05-03
期刊: The Journal of experimental medicine
影响因子: --
作者:
Chandawarkar RY;Wagh MS;Srivastava PK
通讯作者: Srivastava PK