CD91: a receptor for heat shock protein gp96

Nat Immunol. 2000 Aug;1(2):151-5. doi: 10.1038/77835.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / metabolism*
  • Heat-Shock Proteins / metabolism*
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Membrane Glycoproteins / metabolism*
  • Molecular Sequence Data
  • Peptides / immunology
  • Rabbits
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • alpha-Macroglobulins / metabolism*


  • Antigens, Neoplasm
  • Heat-Shock Proteins
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Membrane Glycoproteins
  • Peptides
  • Receptors, Immunologic
  • alpha-Macroglobulins
  • sarcoma glycoprotein gp96 rejection antigens