Cutting edge: receptor-mediated endocytosis of heat shock proteins by professional antigen-presenting cells.
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.
Arnold-Schild
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D
Abteilung Immunologie, Institut für Zellbiologie, Universität Tübingen, Germany.
Hanau
D
D
Spehner
D
D
Schmid
C
C
Rammensee
H G
HG
de la Salle
H
H
Schild
H
H
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D000951:Antigens, Neoplasm / Q000378:metabolism; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism / Q000648:ultrastructure; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis / Q000276:immunology*; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D006046:Gold / Q000378:metabolism; D006183:H-2 Antigens / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007941:Leukemia P388; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*
D000951:Antigens, Neoplasm; D002966:Clathrin; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D006360:Heat-Shock Proteins; D011948:Receptors, Antigen, T-Cell; C052646:sarcoma glycoprotein gp96 rejection antigens; D006046:Gold