Functional domains of HSP70 stimulate generation of cytokines and chemokines, maturation of dendritic cells and adjuvanticity
Functional domains of HSP70 stimulate generation of cytokines and chemokines, maturation of dendritic cells and adjuvanticity
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DOI：
10.1042/bst0320629
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发表时间：
2004-08-01
影响因子：
3.9
通讯作者：
Singh, M
中科院分区：
文献类型：
--
作者：
Lehner, T;Wang, Y;Singh, M
微生物热休克蛋白70（heat-shock protein 70）由三个功能不同的结构域组成：N-末端44 kDa ATP酶部分（氨基酸1-358），随后是18 kDa肽结合结构域（氨基酸359-494）和C-末端10 kDa片段（氨基酸495-609）。这三种不同结构域在刺激单核细胞和树突状细胞中的免疫功能尚未完全确定。然而，C-末端部分（氨基酸359-610）刺激CC趋化因子、IL-12（白细胞介素-12）、TNF α（肿瘤坏死因子α）、NO的产生和树突细胞的成熟，并且还在诱导免疫应答中起佐剂的作用。相比之下，微生物HSP 70的ATP酶结构域大多缺乏这些功能。由于HSP 70的受体是CD 40，其与其CD 40配体构成抗原呈递细胞和T细胞之间相互作用的主要共刺激途径，因此HSP 70可能作为CD 40 L的替代配体发挥作用。HSP 70-CD 40相互作用在非人灵长类动物中已被证明在HIV感染、抗结核分枝杆菌和将耐受转化为免疫中发挥作用。
Microbial HSP70 (heat-shock protein 70) consists of three functionally distinct domains: an N-terminal 44 kDa ATPase portion (amino acids 1-358), followed by an 18 kDa peptide-binding domain (amino acids 359-494) and a C-terminal 10 kDa fragment (amino acids 495-609). Immunological functions of these three different domains in stimulating monocytes and dendritic cells have not been fully defined. However, the C-terminal portion (amino acids 359-610) stimulates the production of CC chemokines, IL-12 (interleukin-12), TNFalpha (tumour necrosis factor alpha), NO and maturation of dendritic cells and also functions as an adjuvant in the induction of immune responses. In contrast, the ATPase domain of microbial HSP70 mostly lacks these functions. Since the receptor for HSP70 is CD40, which with its CD40 ligand constitutes a major costimulatory pathway in the interaction between antigen-presenting cells and T-cells, HSP70 may function as an alternative ligand to CD40L. HSP70-CD40 interaction has been demonstrated in non-human primates to play a role in HIV infection, in protection against mycobacterium tuberculosis and in conversion of tolerance to immunity.