Cross-Presentation of Glycoprotein 96–Associated Antigens on Major Histocompatibility Complex Class I Molecules Requires Receptor-Mediated Endocytosis

摘要: Heat shock proteins (HSPs) like glycoprotein (gp)96 (glucose-regulated protein 94 [grp94]) are able to induce specific cytotoxic T lymphocyte (CTL) responses against cells from which they originate. Here, we demonstrate that for CTL activation by gp96-chaperoned peptides, receptor-mediated uptake of gp96 antigen-presenting (APCs) is required. Moreover, show in both humans and mice, only professional APCs dendritic (DCs), macrophages, B cells, but not bind gp96. The binding saturable can be inhibited using unlabeled molecules. Receptor leads a rapid internalization gp96, colocalizes with endocytosed major histocompatibility complex (MHC) class I II molecules endosomal compartments. Incubation isolated expressing an adenovirus type 5 E1B epitope the DC line D1 results E1B-specific CTLs. This specifically addition irrelevant associated peptides. Our endocytosis MHC I–restricted re-presentation gp96-associated peptides activation; non–receptor-mediated, nonspecific do so. Thus, provide evidence on mechanisms participating cross-presentation antigens cellular origin.