title: Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate.
abstract: Antigen-presenting cells (APCs) internalize antigens and present antigen-derived peptides to T cells. Although APCs have been thought to exhibit a well-developed capacity for lysosomal proteolysis, here we found that they can exhibit two distinct strategies upon antigen encounter. Whereas macrophages contained high levels of lysosomal proteases and rapidly degraded internalized proteins, dendritic cells (DCs) and B lymphocytes were protease-poor, resulting in a limited capacity for lysosomal degradation. Consistent with these findings, DCs in vivo degraded internalized antigens slowly and thus retained antigen in lymphoid organs for extended periods. Limited lysosomal proteolysis also favored antigen presentation. These results help explain why DCs are able to efficiently accumulate, process, and disseminate antigens and microbes systemically for purposes of tolerance and immunity.
authors.affiliation: Department of Cell Biology and Department of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, 333 Cedar Street, Post Office Box 208002, New Haven, CT 06520-8002, USA.
authors.forename: Lélia
authors.initials: L
authors.lastname: Delamarre
authors.forename: Margit
authors.initials: M
authors.lastname: Pack
authors.forename: Henry
authors.initials: H
authors.lastname: Chang
authors.forename: Ira
authors.initials: I
authors.lastname: Mellman
authors.forename: E Sergio
authors.initials: ES
authors.lastname: Trombetta
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D000941:Antigens / Q000378:metabolism*; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis; D049452:Green Fluorescent Proteins / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006735:Horseradish Peroxidase / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000201:enzymology* / Q000648:ultrastructure; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D010447:Peptide Hydrolases / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000276:immunology / Q000378:metabolism; D012260:Ribonucleases / Q000276:immunology / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D000941:Antigens; D049452:Green Fluorescent Proteins; D000949:Histocompatibility Antigens Class II; D006735:Horseradish Peroxidase; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D010447:Peptide Hydrolases; D012259:Ribonuclease, Pancreatic; D012260:Ribonucleases; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C022542:ribonuclease S