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


CONCLUSIONS
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.
Leb
Victoria M
VM
Christian Doppler Laboratory for Immunomodulation, Vienna, Austria.
Jahn-Schmid
Beatrice
B
Kueng
Hans J
HJ
Schmetterer
Klaus G
KG
Haiderer
Daniela
D
Neunkirchner
Alina
A
Fischer
Gottfried F
GF
Hartl
Arnulf
A
Thalhamer
Josef
J
Steinberger
Peter
P
Bohle
Barbara
B
Seed
Brian
B
Pickl
Winfried F
WF
D002460:Cell Line; D003001:Cloning, Molecular; D016207:Cytokines / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics; D015234:HLA-A Antigens / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000379:methods*; D019169:Jurkat Cells; D007668:Kidney / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014771:Virion / Q000235:genetics
D016207:Cytokines; D015234:HLA-A Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C487961:HLA-DRB1*01:01 antigen; D000949:Histocompatibility Antigens Class II