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CUTTING EDGE |
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Abteilung Immunologie, Institut für Zellbiologie, Universität Tübingen, Tübingen, Germany; and
Contrat Jeune Formation Institut National de la Santé et de la Recherche Médicale 94-03, Laboratoire d’Histocompatibilité, Etablissement de Transfusion Sanguine, Strasbourg, France
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.
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