CD91 Is a Common Receptor for Heat Shock Proteins gp96, hsp90, hsp70, and Calreticulin

Immunity. 2001 Mar;14(3):303-13. doi: 10.1016/s1074-7613(01)00111-x.

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