Abstract
Complexes of the heat shock protein gp96 and antigenic peptides are taken up by antigen-presenting cells and presented by MHC class I molecules. In order to explain the unusual efficiency of this process, the uptake of gp96 had been postulated to occur through a receptor, identified recently as CD91. We show here that complexes of peptides with heat shock proteins hsp90, calreticulin, and hsp70 are also taken up by macrophages and dendritic cells and re-presented by MHC class I molecules. All heat shock proteins utilize the CD91 receptor, even though some of the proteins have no homology with each other. Postuptake processing of gp96-chaperoned peptides requires proteasomes and the transporters associated with antigen processing, utilizing the classical endogenous antigen presentation pathway.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Antigen Presentation*
-
Antigens, Neoplasm / metabolism*
-
Bone Marrow
-
Calcium-Binding Proteins / metabolism*
-
Calreticulin
-
Cells, Cultured
-
Cysteine Endopeptidases / metabolism
-
Dendritic Cells / cytology
-
Dendritic Cells / immunology
-
Dendritic Cells / metabolism
-
Gene Deletion
-
HSP70 Heat-Shock Proteins / metabolism*
-
HSP90 Heat-Shock Proteins / metabolism*
-
Histocompatibility Antigens Class I / immunology
-
Humans
-
Low Density Lipoprotein Receptor-Related Protein-1
-
Macrophage-1 Antigen / analysis
-
Macrophages, Peritoneal / immunology
-
Macrophages, Peritoneal / metabolism
-
Mice
-
Multienzyme Complexes / metabolism
-
Nucleocytoplasmic Transport Proteins*
-
Peptides / immunology
-
Peptides / metabolism
-
Proteasome Endopeptidase Complex
-
Protein Binding
-
Proteins / genetics
-
Proteins / metabolism
-
RNA-Binding Proteins*
-
Receptors, Immunologic / metabolism*
-
Ribonucleoproteins / metabolism*
-
Substrate Specificity
-
T-Lymphocytes, Cytotoxic / immunology
-
Tumor Cells, Cultured
-
alpha-Macroglobulins / metabolism
Substances
-
Antigens, Neoplasm
-
Calcium-Binding Proteins
-
Calreticulin
-
HSP70 Heat-Shock Proteins
-
HSP90 Heat-Shock Proteins
-
Histocompatibility Antigens Class I
-
Low Density Lipoprotein Receptor-Related Protein-1
-
Macrophage-1 Antigen
-
Multienzyme Complexes
-
NXF1 protein, human
-
Nucleocytoplasmic Transport Proteins
-
Peptides
-
Proteins
-
RNA-Binding Proteins
-
Receptors, Immunologic
-
Ribonucleoproteins
-
alpha-Macroglobulins
-
sarcoma glycoprotein gp96 rejection antigens
-
Cysteine Endopeptidases
-
Proteasome Endopeptidase Complex