Immune response modulation by recombinant peptides expressed in virus-like particles.
Aspergillus fumigatus, a ubiquitous fungus, is implicated in the pathogenesis of a number of clinically different allergic diseases in man, including allergic bronchopulmonary aspergillosis. Peptide-based immunotherapy may offer an alternative treatment strategy for the management of allergic disease. The objective of this study was to alter the allergen-specific immune response using dominant T cell epitopes of a major A. fumigatus allergen, Asp f2, expressed in yeast as virus-like particles (VLP). The T cell epitopes of Asp f2, recognized in mice with an H-2d background, were determined by producing T-cell hybridomas. Two dominant T cell epitopes, aa60--71 and aa235--249, were identified and expressed in a yeast VLP system. To induce tolerance VLP-peptides were injected subcutaneously into mice previously immunized with recombinant Asp f2. The T cell immune response was abrogated totally in 3 weeks following a single injection of VLP but was restored 2 months later following intranasal antigen exposure. T-cell depletion resulted in the reduction of 20-30% of all antigen-specific immunoglobulin classes. Thus, recombinant peptides expressed in the VLP system can be used successfully in the modulation of Asp f2-induced immune response in mice, although a single administration is not sufficient to maintain a state of tolerance for a long period of time.
Svirshchevskaya
E V
EV
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia. esvir@mail.ibch.ru
Alekseeva
L
L
Marchenko
A
A
Viskova
N
N
Andronova
T M
TM
Benevolenskii
S V
SV
Kurup
V P
VP
D000485:Allergens / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D000818:Animals; D000946:Antigens, Fungal / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D001228:Aspergillosis / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D001232:Aspergillus fumigatus / Q000276:immunology*; D002478:Cells, Cultured / Q000276:immunology; D003888:Desensitization, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005656:Fungal Proteins / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D006825:Hybridomas / Q000276:immunology; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000485:Allergens; D000946:Antigens, Fungal; D005656:Fungal Proteins; D016056:Immunodominant Epitopes; D007376:Interleukin-2; D010455:Peptides; D011993:Recombinant Fusion Proteins; C106810:allergen Asp f 2, Aspergillus fumigatus