T cells induce extended class II MHC compartments in dendritic cells in a Toll-like receptor-dependent manner.
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.
Boes
Marianne
M
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Bertho
Nicolas
N
Cerny
Jan
J
Op den Brouw
Marjolein
M
Kirchhausen
Tomas
T
Ploegh
Hidde
H
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D004705:Endocytosis / Q000235:genetics / Q000276:immunology; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D049452:Green Fluorescent Proteins; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007399:Interphase / Q000276:immunology; D008164:Luminescent Proteins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88; D010455:Peptides / Q000378:metabolism; D011506:Proteins / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010455:Peptides; D011506:Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D048029:TNF Receptor-Associated Factor 6; D051193:Toll-Like Receptors; D049452:Green Fluorescent Proteins