Wang Yufei, Whittall Trevor, McGowan Edward, Younson Justine, Kelly Charles, Bergmeier Lesley A, Singh Mahavir, Lehner Thomas
Mucosal Immunology Unit, Department of Oral Medicine and Pathology, Guy's, King's and St. Thomas' Hospital Medical and Dental Schools, London, United Kingdom.
J Immunol. 2005 Mar 15;174(6):3306-16. doi: 10.4049/jimmunol.174.6.3306.
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.
70 kDa的微生物热休克蛋白（mHSP70）对免疫系统有深远影响，它与树突状细胞（DC）和单核细胞上的CD40受体相互作用以产生细胞因子和趋化因子。mHSP70还可诱导树突状细胞（DC）成熟，因此可作为T细胞上CD40L的替代配体。在本研究中，我们通过用源自mHSP70序列的重叠合成肽（20肽）激活DC，鉴定出一种细胞因子刺激表位（肽407 - 426）。该肽还能显著增强由mHSP70或CD40L刺激的DC成熟。该表位位于HSP70肽结合槽的底部，有五个关键残基。此外，在肽结合槽下游鉴定出一个抑制性表位（p457 - 496），它可抑制由HSP70或CD40L刺激的DC的细胞因子产生和成熟。p38丝裂原活化蛋白激酶磷酸化在替代性CD40 - HSP70途径中至关重要，被p457 - 496抑制，但被p407 - 426增强。
