CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin

Complexes of the heat shock protein gp96 and antigenic peptides are taken u p by antigen-presenting cells and presented by MHC class I molecules. In or der to explain the unusual efficiency of this process, the uptake of gp96 h ad been postulated to occur through a receptor, identified recently as CD91 . We show here that complexes of peptides with heat shock proteins hsp90, c alreticulin, 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 prot easomes and the transporters associated with antigen processing, utilizing the classical endogenous antigen presentation pathway.