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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Leb, Victoria M. Jahn-Schmid, Beatrice Kueng, Hans J. Schmetterer, Klaus G. Haiderer, Daniela Neunkirchner, Alina Fischer, Gottfried F. Hartl, Arnulf Thalhamer, Josef Steinberger, Peter Bohle, Barbara Seed, Brian Pickl, Winfried F. |
| Description | Country affiliation: Austria Author Affiliation: Leb VM ( Christian Doppler Laboratory for Immunomodulation, Vienna, Austria.) |
| Abstract | BACKGROUND: T(H)2 lymphocytes play an important role in the induction and maintenance phase of type I allergy. Modulation of the responses of T(H)2 lymphocytes by novel forms of antigen-presenting platforms may help shape the immune response to allergen and palliate allergic diseases. OBJECTIVE: To present HLA class II/allergen-peptide complexes on virus-like particles (VLPs) and to evaluate their potential to modulate allergen-specific T-cell responses. METHODS: Virus-like particles that express the immunodominant T-cell epitope Art v 1(25-34) of the major mugwort pollen allergen in the context of HLA-DR1 and costimulatory molecules were produced by transfection of 293 cells. The effect of VLPs on IL-2 promoter activity, proliferation, and cytokine production of allergen-specific T cells derived from donors with and without mugwort pollen allergy was determined. RESULTS: Flow-cytometric analyses showed that HLA class II molecules, invariant chain::Art v 1 fusion proteins, and costimulatory molecules were expressed on 293 cells. Biochemical analyses confirmed that these molecules were efficiently targeted to VLPs. The engineered VLPs activated Art v 1-specific T cells in a costimulation-dependent manner. VLPs lacking costimulators induced T-cell unresponsiveness, which was overcome by addition of exogenous IL-2. Costimulation could be provided by CD80, CD86, or CD58 and induced distinct cytokine profiles in allergen-specific T cells. Unlike the other costimulatory molecules, CD58 induced IL-10/IFN-gamma-secreting T cells. CONCLUSION: Virus-like particles represent a novel, modular, acellular antigen-presenting system able to modulate the responses of allergen-specific T cells in a costimulator-dependent fashion. Allergen-specific VLPs show promise as tools for specific immunotherapy of allergic diseases. |
| File Format | HTM / HTML |
| ISSN | 00916749 |
| e-ISSN | 10976825 |
| Journal | Journal of Allergy and Clinical Immunology |
| Issue Number | 1 |
| Volume Number | 124 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2009-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Immunology Hla-dr Antigens Metabolism Pharmacology Histocompatibility Antigens Class Ii Immunology Immunization T-lymphocytes Cell Line Cloning, Molecular Cytokines Genetic Vectors Genetics Hla-a Antigens Hla-drb1 Chains Jurkat Cells Kidney Cytology Drug Effects Virion Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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