CD91: a receptor for heat shock protein gp96

Antigen presenting cells (APCs) can take up exogenous antigenic peptides ch aperoned by heat shock protein gp96 and re-present them through the endogen ous pathway on their major histocompatibility class I molecules. The high e fficiency of this process has been attributed previously to a receptor for gp96 on APCs, The CD91 molecule (also called alpha(2)-macroglobulin recepto r or the low density lipoprotein-related protein) is shown here to be a cel l surface receptor for the heat shock protein gp96, CD91 binds gp96 directl y, rather than through another ligand for CD91. The previously known CD91 l igand, alpha(2)-macroglobulin, inhibits re-presentation of gp96-chaperoned antigenic peptides by macrophages, as do antibodies to CD91. As gp96 is exc lusively intracellular and is released as a result of necrotic but not apop totic cell death, we propose that CD91 acts as a sensor for necrotic cell d eath.