Characterization of a receptor for heat shock protein 70 on macrophages and monocytes

Heat shock proteins (Hsps) and molecular chaperones isolated from tumors or virally infected cells elicit an efficient CD8(+) T cell response against bound antigenic peptides. This immune response is mediated by presentation of the peptides on MHC class I complexes of antigen-presenting cells (APCs) , but the cellular mechanism of this presentation process is not yet unders tood. Here we provide evidence for the existence of a proteinaceous recepto r on the surface of APCs that is specific for mammalian Hsp70. Using a flow cytometry-based assay, saturable binding of Hsp70 to the cell surface of m acrophages and peripheral blood monocytes, but not of lymphocytes, can be d emonstrated. The affinity of the receptor is in the sub-micromolar range (K -d < 100 nM). Only mammalian Hsc70/Hsp70, but not bacterial Hsp70, is bound with high affinity. Subsequent to binding, Hsp70 is taken up by endocytosi s, resulting in an intracellular localization. Our results suggest that rec eptor-mediated endocytosis forms the basis for the demonstrated efficacy of Hsp70-peptide complexes as anti-tumor vaccines.