The scavenger receptor-A (SR-A), originally recognized by its ability to internalize modified lipoproteins, has largely been studied in relation to atherosclerosis as well as innate immunity against pathogen infection. SR-A was recently shown to be a receptor on antigen-presenting cell for heat shock protein (HSP) and was implicated in the crosspresentation of HSP-chaperoned antigens. Here, we show that SR-A is not required for antitumor immunity generated by HSP-based (e.g., grp170) vaccine approaches in vivo.

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 hsp110-rat neu (intracellular domain) heat shock complex vaccine is used to pulse mouse bmDC in vitro, an induction of IFN-c 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.

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