Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells.
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.
Kleijmeer
M
M
Department of Cell Biology, University Medical Center, Institute of Biomembranes and Center for Biomedical Genetics, 3584 CX Utrecht, Netherlands.
Ramm
G
G
Schuurhuis
D
D
Griffith
J
J
Rescigno
M
M
Ricciardi-Castagnoli
P
P
Rudensky
A Y
AY
Ossendorp
F
F
Melief
C J
CJ
Stoorvogel
W
W
Geuze
H J
HJ
D000818:Animals; D017951:Antigen Presentation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D021381:Protein Transport; D022161:Transport Vesicles / Q000378:metabolism*; D015854:Up-Regulation
D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D008565:Membrane Proteins