CD91: a receptor for heat shock protein gp96.
Antigen presenting cells (APCs) can take up exogenous antigenic peptides chaperoned by heat shock protein gp96 and re-present them through the endogenous pathway on their major histocompatibility class I molecules. The high efficiency of this process has been attributed previously to a receptor for gp96 on APCs. The CD91 molecule (also called alpha 2-macroglobulin receptor or the low density lipoprotein-related protein) is shown here to be a cell surface receptor for the heat shock protein gp96. CD91 binds gp96 directly, rather than through another ligand for CD91. The previously known CD91 ligand, alpha 2-macroglobulin, inhibits re-presentation of gp96-chaperoned antigenic peptides by macrophages, as do antibodies to CD91. As gp96 is exclusively intracellular and is released as a result of necrotic but not apoptotic cell death, we propose that CD91 acts as a sensor for necrotic cell death.
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
R J
RJ
Binder
D K
DK
Han
P K
PK
Srivastava
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011817:Rabbits; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism*
D000951:Antigens, Neoplasm; D006360:Heat-Shock Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins; D010455:Peptides; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins; C052646:sarcoma glycoprotein gp96 rejection antigens