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The Journal of Immunology, 2003, 171: 4081-4088.
Copyright © 2003 by The American Association of Immunologists

T Cells Induce Extended Class II MHC Compartments in Dendritic Cells in a Toll-Like Receptor-Dependent Manner 1

Marianne Boes*, Nicolas Bertho*, Jan Cerny{dagger},{ddagger},§, Marjolein Op den Brouw*, Tomas Kirchhausen{dagger},{ddagger} and Hidde Ploegh2,*

* Department of Pathology, {dagger} The Center for Blood Research, and {ddagger} Department of Cell Biology, Harvard Medical School, Boston, MA 02115; and § Faculty of Science, Charles University, Prague, Czech Republic

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.




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