Hsp110 and Grp170, members of the Hsp70 superfamily, bind to scavenger receptor-A and scavenger receptor expressed by endothelial cells-I
✍ Scribed by John G. Facciponte; Xiang-Yang Wang; John R. Subjeck
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 357 KB
- Volume
- 37
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
Heat shock protein 110 (hsp110) and glucose‐regulated protein (grp170) act as anti‐cancer 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 hsp110‐rat neu (intracellular domain) heat shock complex vaccine is used to pulse mouse bmDC in vitro, an induction of IFN‐γ 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.