Abstract
Interaction of Ag-loaded dendritic cells with Ag-specific CD4 T cells induces the formation of long tubular class II MHC-positive compartments that polarize toward the T cell. We show involvement of a Toll-like receptor-mediated signal in this unusual form of intracellular class II MHC trafficking. First, wild-type dendritic cells loaded with LPS-free Ag failed to show formation of class II-positive tubules upon Ag-specific T cell engagement, but did so upon supplementation of the Ag with low concentrations of LPS. Second, Ag-loaded myeloid differentiation factor 88 -deficient dendritic cells failed to form these tubules upon interaction with T cells, regardless of the presence of LPS. Finally, inclusion of a cell-permeable peptide that blocks TNFR-associated factor 6 function, downstream of myeloid differentiation factor 88, blocked T cell-dependent tubulation. A Toll-like receptor-dependent signal is thus required to allow Ag-loaded dendritic cells to respond to T cell contact by formation of extended endosomal compartments. This activation does not result in massive translocation of class II MHC molecules to the cell surface.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Antigens, Differentiation / genetics
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Bone Marrow Cells / cytology
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Bone Marrow Cells / immunology
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cells, Cultured
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Dendritic Cells / cytology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism*
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Endocytosis / genetics
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Endocytosis / immunology
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Endosomes / immunology
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Endosomes / metabolism
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Green Fluorescent Proteins
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Histocompatibility Antigens Class II / biosynthesis*
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / metabolism
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Interphase / immunology
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Luminescent Proteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Knockout
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Microtubules / metabolism
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Myeloid Differentiation Factor 88
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Peptides / metabolism
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Proteins / physiology
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Receptors, Cell Surface / physiology*
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Receptors, Immunologic / deficiency
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Receptors, Immunologic / genetics
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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TNF Receptor-Associated Factor 6
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Toll-Like Receptors
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Differentiation
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Histocompatibility Antigens Class II
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I-A(b) antigen, mouse
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Luminescent Proteins
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Membrane Glycoproteins
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Peptides
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Proteins
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Receptors, Cell Surface
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Receptors, Immunologic
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TNF Receptor-Associated Factor 6
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Toll-Like Receptors
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Green Fluorescent Proteins