Modulation of allergen-specific T-lymphocyte function by virus-like particles decorated with HLA class II molecules

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:124

Article

Leb, Victoria M.²  Jahn-Schmid, Beatrice³  Kueng, Hans J.²  Neunkirchner, Alina²  Fischer, Gottfried F.⁴  Hartl, Arnulf⁵  Thalhamer, Josef⁶  Bohle, Barbara^2,3  Seed, Brian⁷  Pickl, Winfried F.^1,2 

[1] Med Univ Vienna, Inst Immunol, Ctr Physiol Pathophysiol & Immunol, A-1090 Vienna, Austria

[2] Christian Doppler Lab Immunomodulat, Vienna, Austria

[3] Med Univ Vienna, Dept Pathophysiol, Ctr Physiol Pathophysiol & Immunol, A-1090 Vienna, Austria

[4] Med Univ Vienna, Dept Blood Grp Serol, A-1090 Vienna, Austria

[5] Paracelsus Med Univ, Inst Physiol & Pathophysiol, Salzburg, Austria

[6] Salzburg Univ, Div Allergy Immunol, Dept Mol Biol, A-5020 Salzburg, Austria

[7] Harvard Univ, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA

关键词: Artificial APC;    Art v 1;    HLA class II;    mugwort pollinosis;    T-cell modulation;    costimulation;    TCR tg T cells;    type I allergy;    virus-like particles;   

DOI  :  10.1016/j.jaci.2009.04.008

来源: Elsevier

【 摘 要 】

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. (J Allergy Clin Immunol 2009;124:121-8.)

【 授权许可】

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