Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells

  • Monique Kleijmeer
    1Department of Cell Biology, University Medical Center, Institute of Biomembranes and Center for Biomedical Genetics, 3584 CX Utrecht, Netherlands
  • Georg Ramm
    1Department of Cell Biology, University Medical Center, Institute of Biomembranes and Center for Biomedical Genetics, 3584 CX Utrecht, Netherlands
  • Danita Schuurhuis
    2Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, Netherlands
  • Janice Griffith
    1Department of Cell Biology, University Medical Center, Institute of Biomembranes and Center for Biomedical Genetics, 3584 CX Utrecht, Netherlands
  • Maria Rescigno
    3Department of Biotechnology and Bioscience, University of Milano-Bicocca, 20126 Milan, Italy
  • Paola Ricciardi-Castagnoli
    3Department of Biotechnology and Bioscience, University of Milano-Bicocca, 20126 Milan, Italy
  • Alexander Y. Rudensky
    4Howard Hughes Medical Institute, University of Washington, School of Medicine, Seattle, WA 98195
  • Ferry Ossendorp
    4Howard Hughes Medical Institute, University of Washington, School of Medicine, Seattle, WA 98195
  • Cornelis J.M. Melief
    4Howard Hughes Medical Institute, University of Washington, School of Medicine, Seattle, WA 98195
  • Willem Stoorvogel
    1Department of Cell Biology, University Medical Center, Institute of Biomembranes and Center for Biomedical Genetics, 3584 CX Utrecht, Netherlands
  • Hans J. Geuze
    1Department of Cell Biology, University Medical Center, Institute of Biomembranes and Center for Biomedical Genetics, 3584 CX Utrecht, Netherlands

抄録

<jats:p>Immature dendritic cells (DCs) sample their environment for antigens and after stimulation present peptide associated with major histocompatibility complex class II (MHC II) to naive T cells. We have studied the intracellular trafficking of MHC II in cultured DCs. In immature cells, the majority of MHC II was stored intracellularly at the internal vesicles of multivesicular bodies (MVBs). In contrast, DM, an accessory molecule required for peptide loading, was located predominantly at the limiting membrane of MVBs. After stimulation, the internal vesicles carrying MHC II were transferred to the limiting membrane of the MVB, bringing MHC II and DM to the same membrane domain. Concomitantly, the MVBs transformed into long tubular organelles that extended into the periphery of the cells. Vesicles that were formed at the tips of these tubules nonselectively incorporated MHC II and DM and presumably mediated transport to the plasma membrane. We propose that in maturing DCs, the reorganization of MVBs is fundamental for the timing of MHC II antigen loading and transport to the plasma membrane.</jats:p>

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