| 615 |
Dendritic
cell maturation triggers retrograde MHC class II
transport from lysosomes
to the plasma membrane |
Amy
Chow, Derek Toomre, Wendy Garrett & Ira Mellman |
peptide
antigen, T lymphocytes, antigen presentation, major histocompatibility complex class II molecules
(MHC II), endocytosis, green fluorescent protein (GFP) |
To label lysosomes, day 4–5 immature
dendritic cells were…plated for 30min on poly-L-lysine pre-coated number 1.5 coverslips attached
to 35-mm dishes (MatTek).
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confocal
microscopy |
|
|
dendritic |
| |
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 presentation1. Their life cycle includes several
stages characterized by distinct functions and mechanisms of regulation2. Immature dendritic
cells synthesize large amounts of major histocompatibility complex class II molecules (MHC II),
but the ab-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 surface3–10. 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 intact11. 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. |
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