Hsp110 and Grp170, members of the Hsp70 superfamily, bind to scavenger receptor-A expressed by endothelial and scavenger receptor cells-I
Hsp110 and Grp170, members of the Hsp70 superfamily, bind to scavenger receptor-A expressed by endothelial and scavenger receptor cells-I
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DOI：
10.1002/eji.200737127
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发表时间：
2007-08-01
影响因子：
5.4
通讯作者：
Subjeck, John R.
中科院分区：
文献类型：
--
作者：
Facciponte, John G.;Wang, Xiang-Yang;Subjeck, John R.
热休克蛋白110 （hsp110）和葡萄糖调节蛋白（grp170）通过热休克与肿瘤抗原复合物后可作为抗癌疫苗。已经提出抗原呈递细胞上的受体参与热休克蛋白介导的免疫反应。在这里，我们发现hsp110以受体介导的方式与RAW264.7巨噬细胞结合，grp170也是如此。这种hsp110/grp170结合被清道夫受体配体抑制，提示清道夫受体作为结合结构的作用。我们检测了清除率受体A类（SR-A）和内皮细胞- i表达的清除率受体（sreci）。我们发现hsp110/grp170以饱和方式与表达SR-A和srec - i的CHO细胞结合，而清净受体配体抑制这种结合。Hsp110也能饱和结合小鼠骨髓源性树突状细胞（bmDC），并被清道夫受体配体抑制。用hsp110rat新（胞内结构域）热休克复合物疫苗体外刺激小鼠bmDC时，观察到从疫苗免疫小鼠分离的CD8(+) T淋巴细胞诱导ifn - γ分泌。这种免疫反应被清道夫受体配体应用于bmDC抑制。因此，SR-A和srec - 1似乎有助于hsp110和grp170在APC上的结合。一般来说，清道夫受体有助于hsp110蛋白抗原的交叉呈递。
Heat shock protein 110 (hsp110) and glucose-regulated protein (grp170) act as anticancer vaccines when complexed to tumor antigens by heat shock. It has been proposed that receptors on antigen-presenting cells contribute to HSP-mediated immune responses. Here, we show that hsp110 binds in a receptor-mediated manner to RAW264.7 macrophages, as does grp170. This hsp110/grp170 binding is inhibited by scavenger receptor ligands, suggesting a role for scavenger receptors as binding structures. We examined scavenger receptor class A (SR-A) and scavenger receptor expressed by endothelial cells-I (SREC-I). We show that hsp110/grp170 binds to both SR-A- and SREC-I-expressing CHO cells in a saturable manner and scavenger receptor ligands inhibit binding. Hsp110 also saturably binds mouse bone marrow-derived dendritic cells (bmDC) and is inhibited by scavenger receptor ligands. When an hsp110rat neu (intracellular domain) heat shock complex vaccine is used to pulse mouse bmDC in vitro, an induction of IFN-gamma secretion is observed by CD8(+) T lymphocytes isolated from vaccine-immunized mice. This immune response is inhibited by the application of scavenger receptor ligands to bmDC. Thus, SR-A and SREC-I appear to contribute to the binding of hsp110 and grp170 on APC. Scavenger receptors, in general, contribute to the cross-presentation of hsp110-chaperoned protein antigen.