title: Direct stimulation of T lymphocytes by immunosomes: virus-like particles decorated with T cell receptor/CD3 ligands plus costimulatory molecules.
abstract: Many infectious viruses coevolved with the vertebrate immune system. During the assembly of enveloped viruses, lipid ordered domains of the host cell plasma membrane, called lipid rafts, frequently function as a natural meeting point for viral proteins. The role of lipid rafts in the organization of complex combinations of immune receptors during antigen presentation and T cell signaling is widely recognized. In our studies, we determined whether lipid rafts, virus budding, and molecular interactions during T cell activation could be brought into a novel context to create artificial antigen-presenting particles. We show here that cell-free virus-like particles (VLP) expressing a surrogate TCR/CD3 ligand (OKT3scFv) and the costimulator CD80 polyclonally activate human T cells independently of accessory cells. VLP expressing the glycoprotein epitope 33-41 of the lymphocytic choriomeningitis virus in the context of H-2D(b) activate and expand naïve, antigen-specific CD8(+) T lymphocytes and differentiate them into cytotoxic effector cells. Efficient targeting of T cell ligands to lipid rafts and ultimately to VLP is achieved by C-terminal introduction of glycosyl phosphatidyl inositol acceptor sequences, replacing transmembrane and intracellular domains. In this work, basic functions of immunostimulatory molecules meet virus biology and translate into a reductionist antigen-specific T lymphocyte-stimulating vehicle, which we refer to as immunosomes. A large variety of agonistic and antagonistic accessory molecules on genuine antigen-presenting cells may complicate the predictable manipulation of T cells as well as the analysis of selected receptor combinations, making immunosomes potentially useful reagents for such purposes in the future.
authors.affiliation: Institute of Immunology, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Sophia V
authors.initials: SV
authors.lastname: Derdak
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Kueng
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Leb
authors.forename: Alina
authors.initials: A
authors.lastname: Neunkirchner
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Schmetterer
authors.forename: Edith
authors.initials: E
authors.lastname: Bielek
authors.forename: Otto
authors.initials: O
authors.lastname: Majdic
authors.forename: Walter
authors.initials: W
authors.lastname: Knapp
authors.forename: Brian
authors.initials: B
authors.lastname: Seed
authors.forename: Winfried F
authors.initials: WF
authors.lastname: Pickl
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000276:immunology*; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000737:chemistry* / Q000276:immunology / Q000648:ultrastructure; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014771:Virion / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D000939:Epitopes; D017261:Glycosylphosphatidylinositols; D007155:Immunologic Factors; D008024:Ligands; D011948:Receptors, Antigen, T-Cell