title: Exosomes bearing HLA-DR1 molecules need dendritic cells to efficiently stimulate specific T cells.
abstract: Exosomes are small vesicles (60-100 nm) secreted by various cell types upon the fusion of endosomal compartments with the plasma membrane. Exosomes from antigen-presenting cells (APC), such as B lymphocytes and dendritic cells (DC), bear MHC class II molecules. In addition, the injection of DC-derived exosomes was reported to elicit potent T cell responses in vivo. Here, we analyzed the activation of specific T cells by MHC class II-bearing exosomes in vitro. The rat mast cell line, RBL-2H3, was engineered to express human class II molecules uniformly loaded with an antigenic peptide [HLA-DR1-hemagglutinin (HA)]. These cells secreted exosomes bearing DR1 class II molecules upon stimulation by a calcium ionophore or IgE receptor cross-linking. Exosomes bearing DR1-HA(306-318) complexes activated HA/DR1-specific T cells only weakly, whereas the cross-linking of such exosomes to latex beads increased stimulation of specific T cells. By contrast, the incubation of free exosomes with DC resulted in the highly efficient stimulation of specific T cells. Thus, exosomes bearing MHC class II complexes must be taken up by professional APC for efficient T cell activation.
authors.affiliation: INSERM U520, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Vincent-Schneider
authors.forename: Pamela
authors.initials: P
authors.lastname: Stumptner-Cuvelette
authors.forename: Danielle
authors.initials: D
authors.lastname: Lankar
authors.forename: Sabine
authors.initials: S
authors.lastname: Pain
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
authors.forename: Philippe
authors.initials: P
authors.lastname: Benaroch
authors.forename: Christian
authors.initials: C
authors.lastname: Bonnerot
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004140:Dinitrophenols / Q000276:immunology; D015798:HLA-DR1 Antigen / Q000276:immunology*; D006388:Hemagglutinins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008863:Microspheres; D008969:Molecular Sequence Data; D051381:Rats; D012710:Serum Albumin, Bovine / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D004140:Dinitrophenols; D015798:HLA-DR1 Antigen; D006388:Hemagglutinins; D000949:Histocompatibility Antigens Class II; D007476:Ionophores; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E; D015759:Ionomycin