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dc.contributor.authorDerdak, Sophia V.
dc.contributor.authorKueng, Hans J.
dc.contributor.authorLeb, Victoria M.
dc.contributor.authorNeunkirchner, Alina
dc.contributor.authorSchmetterer, Klaus G.
dc.contributor.authorBielek, Edith
dc.contributor.authorMajdic, Otto
dc.contributor.authorKnapp, Walter
dc.contributor.authorSeed, Brian
dc.contributor.authorPickl, Winfried F.
dc.date.accessioned2019-10-17T05:19:16Z
dc.date.issued2006
dc.identifier.citationDerdak, S. V., H. J. Kueng, V. M. Leb, A. Neunkirchner, K. G. Schmetterer, E. Bielek, O. Majdic, W. Knapp, B. Seed, and W. F. Pickl. 2006. “Direct Stimulation of T Lymphocytes by Immunosomes: Virus-like Particles Decorated with T Cell Receptor/CD3 Ligands plus Costimulatory Molecules.” Proceedings of the National Academy of Sciences 103 (35). Proceedings of the National Academy of Sciences: 13144–49. doi:10.1073/pnas.0602283103.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41555779*
dc.description.abstractMany 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 naive, 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.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleDirect stimulation of T lymphocytes by immunosomes: Virus-like particles decorated with T cell receptor/CD3 ligands plus costimulatory molecules
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorSeed, Brian::3ccd6c0058cbef488b937e21cb148e0d::600
dc.date.available2019-10-17T05:19:16Z
dash.workflow.comments1Science Serial ID 89908
dc.identifier.doi10.1073/pnas.0602283103
dash.source.volume103;35
dash.source.page13144


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