Identification of Stimulating and Inhibitory Epitopes within the Heat Shock Protein 70 Molecule That Modulate Cytokine Production and Maturation of Dendritic Cells 1
Identification of Stimulating and Inhibitory Epitopes within the Heat Shock Protein 70 Molecule That Modulate Cytokine Production and Maturation of Dendritic Cells 1
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DOI：
10.4049/jimmunol.174.6.3306
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发表时间：
2005-03
期刊：
影响因子：
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通讯作者：
Yufei Wang;T. Whittall;E. McGowan;J. Younson;C. Kelly;L. Bergmeier;Mahavir Singh;T. Lehner
中科院分区：
文献类型：
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作者：
Yufei Wang;T. Whittall;E. McGowan;J. Younson;C. Kelly;L. Bergmeier;Mahavir Singh;T. Lehner
70 kDa 微生物热休克蛋白 (mHSP70) 对免疫系统具有深远影响，与 DC 和单核细胞上的 CD40 受体相互作用，产生细胞因子和趋化因子。 mHSP70 还可诱导树突细胞 (DC) 成熟，从而充当 T 细胞上 CD40L 的替代配体。在这项研究中，我们通过使用源自 mHSP70 序列的重叠合成肽（20 聚体）激活 DC，鉴定了细胞因子刺激表位（肽 407-426）。该肽还显着增强 mHSP70 或 CD40L 刺激的 DC 成熟。该表位位于 HSP70 肽结合沟的底部，具有 5 个关键残基。此外，在肽结合沟下游发现了一个抑制性表位（p457-496），该表位抑制 HSP70 或 CD40L 刺激的 DC 的细胞因子产生和成熟。 p38 MAP 激酶磷酸化在 CD40-HSP70 替代途径中至关重要，并被 p457-496 抑制，但被 p407-426 增强。
The 70-kDa microbial heat shock protein (mHSP70) has a profound effect on the immune system, interacting with the CD40 receptor on DC and monocytes to produce cytokines and chemokines. The mHSP70 also induces maturation of dendritic cells (DC) and thus acts as an alternative ligand to CD40L on T cells. In this investigation, we have identified a cytokine-stimulating epitope (peptide 407–426), by activating DC with overlapping synthetic peptides (20-mers) derived from the sequence of mHSP70. This peptide also significantly enhances maturation of DC stimulated by mHSP70 or CD40L. The epitope is located at the base of the peptide-binding groove of HSP70 and has five critical residues. Furthermore, an inhibitory epitope (p457–496) was identified downstream from the peptide-binding groove that inhibits cytokine production and maturation of DC stimulated by HSP70 or CD40L. The p38 MAP kinase phosphorylation is critical in the alternative CD40-HSP70 pathway and is inhibited by p457–496 but enhanced by p407–426.