Cutting edge: Receptor-mediated endocytosis of heat shock proteins by professional antigen-presenting cells

Immunization with heat shock proteins (HSPs) induces Ag-specific CTL respon ses. The specificity of the immune response is based on peptides associated with HSPs, To investigate how exogenous HSP/peptide complexes gain access to the MHC class I-restricted Ag presentation pathway, we incubated the mon ocytic cell line P388D1 and the dendritic cell line D2SC/1 with gold-labele d HSPs gp96 and HSC70, We show that HSPs bind specifically to the surface o f these APCs and are internalized spontaneously by receptor-mediated endocy tosis, demonstrating the existence of specific receptors for HSPs on these cells. In addition, we observe colocalization of internalized HSPs and surf ace MHC class I molecules in early and late endosomal structures. These fin dings provide possible explanations for the immunogenicity of HSP/peptide c omplexes and for the transfer of HSP-associated peptides onto MHC class I m olecules.