SREC-1 expression in dendritic cells requires TLR signaling and mediates the immune functions of Hsp70 Free

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Heat shock proteins play an unusual role in immunosurveiIlance in capturing intracellular antigens, ferrying them to antigen presenting cells (APC) and mediating cross priming of T lymphocytes. However the salient mechanisms are still obscure. We show that Hsp70 mediated cross priming involves binding to scavenger receptor SREC-1 on the surface of dendritic cells (DC). Exposure of DC to Hsp70-peptide complexes leads to Hsp70 uptake as well as induction of SREC-1 mRNA and cell surface protein expression. SREC-1 expression was dependent on toll-like receptor/MyD88 signaling and ablation of this pathway inhibited SREC-1 expression, Hsp70 binding and cross priming of T lymphocytes. Furthermore, the expression of SREC-1 was correlated with the induction of tumor antigen-specific T cells. Killing of murine breast carcinoma cells by immunization with Hsp70-based vaccines was dependent on SREC-1 expression in host dendritic cells.