Scavenger receptors and heat-shock protein-mediated antigen cross-presentation.
Heat-shock proteins (HSPs) induce protective cytotoxic immune responses against tumour antigens. This property is related to their ability to bind to and to be internalized by DC (dendritic cells) before gaining access to the MHC class I processing pathway, a process called antigen cross-presentation. This process requires internalization of the antigen by DC via endocytic receptors. Owing to their particular immune properties, several studies were focused on the identification of HSP-binding elements on DC. We and others have reported that scavenger receptors are the main HSP-binding structures on human DC and have identified LOX-1 as one of these molecules. The binding of human Hsp70 to DC and the in vitro Hsp70-mediated antigen cross-presentation are inhibited by an anti-LOX-1 monoclonal antibody. In vivo, targeting LOX-1 with a tumour antigen using an anti-LOX-1 monoclonal antibody induces antitumour immunity. Thus scavenger receptors are certainly new promising targets for cancer immunotherapy.
Unité INSERM U564, University Hospital of Angers, 4, rue Larrey, F-49933 Angers, France. yves.delneste@med.univ-angers.fr
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Delneste
D000222:Adaptation, Physiological / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D003429:Cross Reactions; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D011971:Receptors, Immunologic / Q000378:metabolism / Q000502:physiology*; D051116:Receptors, Scavenger; D051127:Scavenger Receptors, Class E
D000941:Antigens; D006360:Heat-Shock Proteins; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051127:Scavenger Receptors, Class E