A B Cell Epitope Peptide Derived from the Major Grass Pollen Allergen Phl p 1 Boosts Allergen-Specific Secondary Antibody Responses without Allergen-Specific T Cell Help

Narayanan, Meena; Freidl, Raphaela; Focke‐Tejkl, Margarete; Baranyi, Ulrike; Wekerle, Thomas; Valenta, Rudolf; Linhart, Birgit

doi:10.4049/jimmunol.1501741

Cited by 13 publications

(11 citation statements)

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“…The absolute requirement of cognate T cell help for boosting an established allergen-specific IgE response has been challenged by several recent findings. In mice, using oligomeric B cell epitope-derived peptides for immunization in the absence of any adjuvants, a boost in allergen-specific IgE responses in the absence of any detectable allergen-specific T cell response was observed (69). Furthermore, blockage of co-stimulation capable of inhibiting the primary allergic sensitization of mice had no effect on re-challenge in an already established allergen-specific immune response (70).…”

Section: Role Of Allergen-specific Antibodies In the Natural Course Omentioning

confidence: 99%

Allergen-Specific Antibodies Regulate Secondary Allergen-Specific Immune Responses

et al. 2019

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Immunoglobulin E (IgE)-associated allergy is the most common immunologically-mediated hypersensensitivity disease. It is based on the production of IgE antibodies and T cell responses against per se innocuous antigens (i.e., allergens) and subsequent allergen-induced inflammation in genetically pre-disposed individuals. While allergen exposure in sensitized subjects mainly boosts IgE production and T cell activation, successful allergen-specific immunotherapy (AIT) induces the production of allergen-specific IgG antibodies and reduces T cell activity. Under both circumstances, the resulting allergen-antibody complexes play a major role in modulating secondary allergen-specific immune responses: Allergen-IgE complexes induce mast cell and basophil activation and perpetuate allergen-specific T cell responses via presentation of allergen by allergen presenting cells to T cells, a process called IgE-facilitated antigen presentation (FAP). In addition, they may induce activation of IgE memory B cells. Allergen-induced production of specific IgGs usually exerts ameliorating effects but under certain circumstances may also contribute to exacerbation. Allergen-specific IgG antibodies induced by AIT which compete with IgE for allergen binding (i.e., blocking IgG) inhibit formation of IgE-allergen complexes and reduce activation of effector cells, B cells and indirectly T cells as FAP is prevented. Experimental data provide evidence that by binding of allergen-specific IgG to epitopes different from those recognized by IgE, allergen-specific IgG may enhance IgE-mediated activation of mast cells, basophils and allergen-specific IgE+ B cells. In this review we provide an overview about the role of allergen-specific antibodies in regulating secondary allergen-specific immune responses.

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Section: Role Of Allergen-specific Antibodies In the Natural Course Omentioning

confidence: 99%

Allergen-Specific Antibodies Regulate Secondary Allergen-Specific Immune Responses

et al. 2019

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“…These conjugates harness alternative T-helper responses because of the carrier protein, thereby generating protective allergen-specific IgG responses without IgE stimulation. 128 BM-32 is a promising recombinant fusion protein in which grass pollen B-cell epitopes have been fused with hepatitis pre-S protein. A recent environmental chamber study reported modest benefit compared with placebo, although this did not reach statistical significance.…”

Section: B-cell Peptide Immunotherapymentioning

confidence: 99%

New approaches to allergen immunotherapy

Gunawardana

Durham

2018

Annals of Allergy, Asthma & Immunology

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Novel routes of immunotherapy, use of modified allergens, and combination of allergens with immunostimulatory adjuvants or immune modifiers have been developed to augment downregulation of T-helper cell type 2 immunity and/or induce "protective" blocking antibodies. Although these strategies have permitted shortened courses, confirmatory phase 3 trials are required to confirm efficacy and safety and head-to-head trials are required for comparative efficacy. Currently, subcutaneous and sublingual immunotherapies using in-house standardized crude extracts remain the only approaches proved to induce long-term tolerance.

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“…Allergenicity depends upon IgE binding activity. IgE epitopes, also known as B cell epitopes, are the sites where serum IgEs bind allergens to induce inflammatory reactions [13, 14 ]. Allergen IgE epitope analysis results can provide a good indicator of patients’ allergy sensitivities and help to predict clinical severity and tolerance development potential [15 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of immunodominant IgE binding epitopes of Der p 24, a major allergen of Dermatophagoides pteronyssinus

Cai

Chen

Zhang

et al. 2019

Clin Transl Allergy

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Background The identification of house dust mite (HDM) allergens and epitopes is important for allergy diagnosis and treatment. We sought to identify the Dermatophagoides pteronyssinus group 24 allergen (Der p 24) and to identify its immunodominant IgE epitope(s). Methods Der p 24 cDNA was cloned and expressed in a pET expression system. The IgE binding activity of purified recombinant (r)Der p 24 was evaluated by western blotting. Truncated Der p 24 proteins and overlapping synthetic polypeptides were subjected to IgE binding assays. Balb/c mice were immunized to investigate IgE epitope induction of IgE production. IgE binding of the 32 N-terminal residues of Der p 24 was compared to other Der p epitopes in enzyme-linked immunosorbent assays and dot blot assays. Human skin prick tests (SPTs) were performed. Results We cloned and expressed Der p 24 cDNA (GenBank accession no. KP893174.1). HDM allergic sera bound rDer p 24 in vitro and 5/10 HDM allergic patients (50%) had positive SPT reactions to rDer p 24. The immunodominant IgE epitope of Der p 24 was localized to the N-terminal 32-residue region, which produced a high specific IgE antibody titer in vivo and promoted mast cell β-hexosaminidase release. The IgE binding activity this N-terminal epitope of Der p 24 was stronger than that of Der p 1 or Der p 2 IgE epitopes. Conclusions We identified Der p 24 as a major HDM allergen with strong IgE binding activity via an immunodominant IgE epitope in the N-terminal 32-residue region, which triggers IgE production in vivo. The identified Der p 24 epitope may support HDM allergy diagnosis and treatment.

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A B Cell Epitope Peptide Derived from the Major Grass Pollen Allergen Phl p 1 Boosts Allergen-Specific Secondary Antibody Responses without Allergen-Specific T Cell Help

Cited by 13 publications

References 50 publications

Allergen-Specific Antibodies Regulate Secondary Allergen-Specific Immune Responses

Allergen-Specific Antibodies Regulate Secondary Allergen-Specific Immune Responses

New approaches to allergen immunotherapy

Identification of immunodominant IgE binding epitopes of Der p 24, a major allergen of Dermatophagoides pteronyssinus

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