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

J Immunol. 1999 Apr 1;162(7):3757-60.


Immunization with heat shock proteins (HSPs) induces Ag-specific CTL responses. 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 monocytic cell line P388D1 and the dendritic cell line D2SC/1 with gold-labeled HSPs gp96 and HSC70. We show that HSPs bind specifically to the surface of these APCs and are internalized spontaneously by receptor-mediated endocytosis, demonstrating the existence of specific receptors for HSPs on these cells. In addition, we observe colocalization of internalized HSPs and surface MHC class I molecules in early and late endosomal structures. These findings provide possible explanations for the immunogenicity of HSP/peptide complexes and for the transfer of HSP-associated peptides onto MHC class I molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism*
  • Antigen-Presenting Cells / ultrastructure
  • Antigens, Neoplasm / metabolism
  • Cell Line
  • Clathrin / metabolism
  • Clathrin / ultrastructure
  • Coated Pits, Cell-Membrane / metabolism
  • Coated Pits, Cell-Membrane / ultrastructure
  • Endocytosis / immunology*
  • Endosomes / metabolism
  • Endosomes / ultrastructure
  • Gold / metabolism
  • H-2 Antigens / metabolism
  • Heat-Shock Proteins / metabolism*
  • Leukemia P388
  • Mice
  • Receptors, Antigen, T-Cell / physiology*


  • Antigens, Neoplasm
  • Clathrin
  • H-2 Antigens
  • H-2K(K) antigen
  • Heat-Shock Proteins
  • Receptors, Antigen, T-Cell
  • sarcoma glycoprotein gp96 rejection antigens
  • Gold