Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate

Science. 2005 Mar 11;307(5715):1630-4. doi: 10.1126/science.1108003.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigen-Presenting Cells / enzymology*
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism
  • Antigens / metabolism*
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cells, Cultured
  • Dendritic Cells / enzymology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Endocytosis
  • Green Fluorescent Proteins / immunology
  • Green Fluorescent Proteins / metabolism
  • Histocompatibility Antigens Class II / immunology
  • Horseradish Peroxidase / immunology
  • Horseradish Peroxidase / metabolism
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / enzymology
  • Lymphoid Tissue / immunology
  • Lysosome-Associated Membrane Glycoproteins
  • Lysosomes / enzymology*
  • Lysosomes / ultrastructure
  • Macrophages / enzymology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C3H
  • Peptide Hydrolases / metabolism*
  • Ribonuclease, Pancreatic / immunology
  • Ribonuclease, Pancreatic / metabolism
  • Ribonucleases / immunology
  • Ribonucleases / metabolism

Substances

  • Antigens
  • Histocompatibility Antigens Class II
  • Lamp1 protein, mouse
  • Lysosome-Associated Membrane Glycoproteins
  • Membrane Glycoproteins
  • Green Fluorescent Proteins
  • Horseradish Peroxidase
  • Ribonucleases
  • Ribonuclease, Pancreatic
  • ribonuclease S
  • Peptide Hydrolases