Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane.
Central to the initiation of immune responses is recognition of peptide antigen by T lymphocytes. The cell biology of dendritic cells makes them ideally suited for the essential process of antigen presentation. Their life cycle includes several stages characterized by distinct functions and mechanisms of regulation. Immature dendritic cells synthesize large amounts of major histocompatibility complex class II molecules (MHC II), but the alpha beta-dimers are targeted to late endosomes and lysosomes (often referred to as MHC class II compartments) where they reside unproductively with internalized antigens. After exposure to microbial products or inflammatory mediators, endocytosis is downregulated, the expression of co-stimulatory molecules is enhanced, and newly formed immunogenic MHC II-peptide complexes are transported to the cell surface. That these MHC II molecules reach the surface is surprising, as the lysosomes comprise the terminal degradative compartment of the endocytic pathway from which exogenous components generally cannot be recovered intact. Here we have visualized this pathway in live dendritic cells by video microscopy, using cells expressing MHC II tagged with green fluorescent protein (GFP). We show that on stimulation, dendritic cells generate tubules from lysosomal compartments that go on to fuse directly with the plasma membrane.
Chow
Amy
A
Department of Cell Biology and Section of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, 333 Cedar Street, PO Box 208002, New Haven, Connecticut 06520-8002, USA.
Toomre
Derek
D
Garrett
Wendy
W
Mellman
Ira
I
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018715:Microscopy, Video; D021381:Protein Transport; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D000949:Histocompatibility Antigens Class II; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins