Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation.
Some exogenous antigens, such as heat shock proteins or apoptotic bodies, gain access to the MHC class I processing pathway and initiate CTL responses, a process called cross-priming. To be efficient in vivo, this process requires endocytosis of the antigen by dendritic cells via receptors which remain unidentified. Here, we report that scavenger receptors are the main HSP binding structures on human dendritic cells and identify LOX-1 as one of these molecules. A neutralizing anti-LOX-1 mAb inhibits Hsp70 binding to dendritic cells and Hsp70-induced antigen cross-presentation. In vivo, to target LOX-1 with a tumor antigen using an anti-LOX-1 mAb induces antitumor immunity. Thus, the scavenger receptor LOX-1 is certainly a promising target for cancer immunotherapy.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017951:Antigen Presentation / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000276:immunology; D019921:Biotinylation; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D006183:H-2 Antigens / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000276:immunology / Q000378:metabolism; D013945:Thymoma / Q000276:immunology / Q000628:therapy; D013953:Thymus Neoplasms / Q000276:immunology / Q000628:therapy; D014162:Transfection
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D018840:HSP70 Heat-Shock Proteins; D011993:Recombinant Fusion Proteins; C049877:maleylalbumin; D012710:Serum Albumin, Bovine; D010047:Ovalbumin