title: Immunological synapse formation licenses CD40-CD40L accumulations at T-APC contact sites.
abstract: The maintenance of tolerance is likely to rely on the ability of a T cell to polarize surface molecules providing "help" to only specific APCs. The formation of a mature immunological synapse leads to concentration of the TCR at the APC interface. In this study, we show that the CD40-CD154 receptor-ligand pair is also highly concentrated into a central region of the synapse on mouse lymphocytes only after the formation of the TCR/CD3 c-SMAC. Concentration of this ligand was strictly dependent on TCR recognition, the binding of ICAM-1 to T cell integrins and the presence of an intact cytoskeleton in the T cells. This may provide a novel explanation for the specificity of T cell help directing the help signal to the site of Ag receptor signal. It may also serve as a site for these molecular aggregates to coassociate and/or internalize alongside other signaling receptors.
authors.affiliation: Department of Pathology, University of California, San Francisco, CA 94143, USA.
authors.forename: Judie
authors.initials: J
authors.lastname: Boisvert
authors.forename: Samuel
authors.initials: S
authors.lastname: Edmondson
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Krummel
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D023201:CD40 Ligand / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology*; D002999:Clone Cells; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008164:Luminescent Proteins / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008806:Mice, Inbred AKR; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010957:Plasmids; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D019013:CD40 Antigens; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008164:Luminescent Proteins; D010446:Peptide Fragments; D017260:Receptor-CD3 Complex, Antigen, T-Cell; C054562:yellow fluorescent protein, Bacteria; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand