Requirements for T cell-polarized tubulation of class II+ compartments in dendritic cells.
Activation of naive CD4 T cells by dendritic cells requires the sequential interaction of many TCR molecules with peptide-class II complexes of the appropriate specificity. Such interaction results in morphological transformation of class II MHC-containing endosomal compartments. In this study, we analyze the requirements for long tubular endosomal structures that polarize toward T cell contact sites using dendritic cells from I-A(b) class II -enhanced green fluorescent protein knock-in mice and I-A(b)-restricted CD4 T cells specific for OVA. Clustering of membrane proteins and ligation of T cell adhesion molecules LFA-1 and CD2 are involved in induction of endosomal tubulation. Activation of T cells increases their ability to induce class II-enhanced green fluorescent protein-positive tubules in dendritic cells, in part through up-regulation of CD40 ligand. Remarkably, and in stark contrast with the result obtained with dendritic cells loaded with intact OVA, OVA peptide added to dendritic cells failed to evoke T cell-polarized endosomal tubulation even though both conditions allowed T cell stimulation. These results suggest the existence of microdomains on the membrane of dendritic cells that allow Ag-specific T cells to evoke tubulation in the dendritic cell.
Bertho
Nicolas
N
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Cerny
Jan
J
Kim
You-Me
YM
Fiebiger
Edda
E
Ploegh
Hidde
H
Boes
Marianne
M
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000096:biosynthesis / Q000502:physiology; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D011992:Endosomes / Q000276:immunology* / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000502:physiology; D049452:Green Fluorescent Proteins; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000502:physiology
D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; D008164:Luminescent Proteins; D023201:CD40 Ligand; D049452:Green Fluorescent Proteins