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  • 1
    Electronic Resource
    Electronic Resource
    Phage-displayed Bet mim 1, a mimotope of the major birch pollen allergen Bet v 1, induces B cell responses to the natural antigen using bystander T cell help (2002)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background and objective In previous studies we have generated mimotopes of Bet v 1, the major birch pollen allergen, by biopannings of phage-display random peptide libraries. In the present study, we analysed the humoral and cellular immune response to Bet v 1-mimotopes.Methods The mimotope CFPYCYPSESA, designated Bet mim 1, was used for intraperitoneal immunizations of BALB/c mice in phage-displayed form. For examination of the humoral immune response, enzyme-linked immunosorbent assay (ELISA) experiments were applied. Stimulation capacities were investigated in cultured mouse splenocytes and in humoral Bet v 1-specific T cell clones.Results We demonstrated that the Bet mim 1-induced murine antibody response against Bet v 1 was predominated by the IgG1 isotype. In these mice only the phage-displayed mimotopes, but neither the allergen nor the synthetic Bet mim 1-mimotopes were able to stimulate proliferation of cultured splenocytes. Using Bet v 1-specific T cell clones of allergic patients, phage-displayed and synthetic mimotopes were unable to stimulate T cell proliferation. Moreover, tolerance induction to Bet v 1 in mice by intranasal administration of Bet mim 1-phages or Bet mim 1-peptide failed.Conclusion Taking these results together, our data indicate that Bet mim 1 mimics a Bet v 1-epitope on the B cell but not on the T cell level. We suggest that the phage itself is responsible for the recruitment of T cells providing bystander help in the formation of a mimotope-specific humoral response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2002.01527.x
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  • 2
    Electronic Resource
    Electronic Resource
    Immunological changes during specific immunotherapy of grass pollen allergy: reduced lymphoproliferative responses to allergen and shift from TH2 to TH1 in T-cell clones specific for Phi p 1, a major grass pollen allergen (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 27 (1997), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background and Objective The mechanisms operative in specific immunotherapy (SIT) of Type I allergy are not completely understood. In the present study we evaluated immunological changes during SIT in pollinosis.Method Eight patients suffering from pollinosis (monosensitized to grass pollen) were treated with conventional SIT. All subjects had IgE specific for Phi p 1. a major allergen of timothy grass. In vitro changes in the immunological reactivity to grass pollen extract and to recombinant Phi p 1 were evaluated. Subjects were examined at three occasions: before, after 3 months and after I year of SIT.Results Serological analysis revealed a marked increase of grass pollen- and Phi p 1-specific IgG, titres of specific IgE did not change significantly. Lymphoproliferative responses to grass pollen extract and rPhl p 1 were reduced already after 3 months of treatment. Accordingly, the cloning efficiency for Ph1 p 1-specific T-cell clones (TCC) dropped markedly in all patients. The majority of allergen-specific TCC raised before SIT revealed a TH2-like pattern of cytokine production. TCC established after SIT revealed TH1 characteristics. This shift was due to a decrease in IL-4 rather than an increase in IFN-production by T cells. Investigations of the epitopes recognized by T cells before and after SIT did not reveal the outgrowth of new (ldquo;protecting”) specificities. We could not observe induction of allergen-speeific CD8+ lymphocytes (supressor cells).Conclusion Our data indicate that — on the level of TH lymphocytes — SIT induces tolerance to the allergen and a modulation of the cytokine pattern produced in response to allergen stimulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1997.tb01252.x
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  • 3
    Electronic Resource
    Electronic Resource
    Non-anaphylactic surface-exposed peptides of the major birch pollen allergen, Bet v 1, for preventive vaccination (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 34 (2004), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Almost 100 million allergic patients are sensitized to the major birch pollen allergen, Bet v 1, a 17 kDa protein containing most of the IgE epitopes present in pollens of trees belonging to the Fagales order and plant-derived food.Objective Our aim was to develop an approach for the rational design of B cell epitope-derived, non-allergenic peptide allergy vaccines.Methods According to the three-dimensional (3-D) structure of birch pollen allergen, Bet v 1, six peptides comprising 25–32 preferably solvent-exposed amino acids were synthesized.Results Because of lack of secondary structure, the peptides showed no allergenic activity in allergic patients. In a mouse model of birch pollen allergy, peptide vaccination induced Bet v 1-specific IgG and prevented IgE-mediated allergic sensitization to Bet v 1. The protective role of peptide-induced blocking antibodies is demonstrated by inhibition of allergic patients IgE binding to the allergen and by blocking of allergen-induced basophil degranulation.Conclusion Our results indicate the mechanistic importance of blocking antibodies for allergy vaccination and present a B cell epitope-based approach for the rational design of safe peptide allergy vaccines whenever the structure of the disease-eliciting allergen is known.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.02081.x
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  • 4
    Electronic Resource
    Electronic Resource
    Mucosal tolerance as therapy of type I allergy: intranasal application of recombinant Bet v 1, the major birch pollen allergen, leads to the suppression of allergic immune responses and airway inflammation in sensitized mice (2002)
    Oxford, UK : Blackwell Science, Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Several studies have demonstrated that mucosal administration of soluble antigens can prevent the onset or reduce the severity of certain autoimmune diseases or allergies. Few studies exist showing the efficacy of mucosal tolerance for therapy of such diseases.Objective The aim of the present study was to modulate an allergic immune response by intranasal antigen administration in an already sensitized organism.Methods A murine model of allergic asthma to birch pollen (BP) and its major allergen Bet v 1 was utilized. Sensitized mice were intranasally treated with recombinant (r)Bet v 1 in different concentrations and at different intervals. On the day the mice were killed, blood and bronchoalveolar lavage fluids were taken and immediate type I skin tests were performed. T cell proliferation and cytokine production (interleukin (IL)-5, interferon (IFN)-γ) were measured in spleen and lung cell cultures.Results Mucosal treatment with rBet v 1 (3 × 50 µg in 4 day intervals) led to a reduction of type I skin reactions, suppressed immunoglobulin (Ig)G1/IgE antibody levels and markedly decreased IL-5 and IFN-γ production in vitro in spleen and lung cell cultures. Moreover, lung inflammation (i.e. eosinophilia and IL-5 levels in bronchoalveolar lavage fluids) was significantly suppressed by the treatment.Conclusion Our results demonstrate that intranasal treatment with rBet v 1 reduced systemic allergic immune responses as well as airway inflammation in BP-sensitized mice. We therefore suggest that mucosal tolerance induction with recombinant allergens could be a promising concept for the therapy of allergic diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0022-0477.2001.01214.x
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  • 5
    Electronic Resource
    Electronic Resource
    Sensitization and development of tolerance via the gut (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Pediatric allergy and immunology 4 (1993), S. 0 
    Details
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1399-3038.1993.tb00326.x
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  • 6
    Electronic Resource
    Electronic Resource
    VITAMIN A DEFICIENCY INCREASES INFLAMMATORY RESPONSES (1996)
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 44 (1996), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The authors studied the influence of vitamin A deficiency on immediate and delayed type hypersensitivity as well as granulocyte-mediated inflammatory reactions in vitamin A depleted and control rats. The number of circulating leucocytes was 43% higher in the vitamin A deficient than in the control animals. The leucocytosis was a result of a general increase of white blood cells and was not due to an increase in one particular type. The ratio between CD4+ and CD8+ T cells was unchanged. The vitamin A deficient rats had a four times higher T-cell proliferative response and a two times higher interferon-γ production in vitro than the control animals. In accordance, the DTH reaction was consistently higher in the vitamin A deficient rats. The granulocyte dependent inflammation, induced by olive oil injection, was also strongly enhanced in the vitamin A deficient rats compared with the controls. In addition, the spontaneous release of nitric oxide from the peritoneal phagocytes was five times higher in the vitamin A deficient animals. The number of peritoneal mast cells was about one and a half times higher in the vitamin A deficient than in the control animals. The density of IgE-receptors on the mast cells, the IgE receptor occupancy and the histamine release from the mast cells did not differ between the groups, however. The vitamin A deficient immunized rats displayed a consistently stronger immediate skin reaction after intracutaneous antigen injection than the immunized control rats, despite lower IgE antibody levels. The skin reaction after intracutaneous injection of histamine was also significantly greater in the deficient animals. Despite the stronger reaction to antigen and histamine, the passive cutaneous anaphylaxis reaction was lower in the vitamin A deficient rats. In conclusion the study shows that vitamin A deficiency aggravates the clinical manifestations of inflammatory reactions. Thus, vitamin A deficiency might lead to a higher risk of acquiring irreversible tissue damage and disabling destruction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.1996.d01-351.x
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