Highly heterogeneous Phl p 5-specific T cells from patients with allergic rhinitis differentially recognize recombinant Phl p 5 isoallergens☆☆☆

Würtzen, Peter Adler; Wissenbach, Margit; Ipsen, Henrik; Bufe, Albrecht; Arnved, J.; Neerven, R. J. Joost van

doi:10.1016/s0091-6749(99)70122-3

Cited by 23 publications

(29 citation statements)

References 41 publications

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“…This renders it unlikely that the predominant HLA-DQ restriction of αs1-casein epitopes is caused by alternative HLA expression at the site of allergen take-up. T cell epitopes in other (food) allergens were previously found to be predominantly restricted to HLA-DR [9,10,11,12,13]. In contrast, the food antigen gliadin is well known for its HLA-DQ-restricted epitopes.…”

Section: Discussionmentioning

confidence: 99%

“…To estimate the functional relevance of an association between an HLA genotype and an allergic phenotype, it is necessary to determine the HLA restriction of the most prominent T cell epitopes in the allergen(s). Previously, a predominant HLA-DR restriction was found for T cell epitopes in the respiratory allergens cat dander [9] and grass pollen (Phl p 5) [10], as well as in the food allergens ovalbumin [11], peanut [12] and β-lactoglobulin, a cow’s milk allergen [13]. …”

Section: Introductionmentioning

confidence: 99%

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Role of Human Leucocyte Antigen DQ in the Presentation of T Cell Epitopes in the Major Cow’s Milk Allergen αs1-Casein

Ruiter

Rozemuller²,

Dijk³

et al. 2007

Int Arch Allergy Immunol

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Background: Little is known about the association between human leucocyte antigen (HLA) and cow’s milk allergy (CMA). The aim of the present study was to determine the HLA restriction of T cell clones (TCCs) specific to αs1-casein, the most abundant milk protein, and to study possible HLA class II allele associations with CMA. Methods: αs1-Casein-specific TCCs were derived from 6 children with CMA, 9 atopic children without CMA and 5 non-atopic children. T cell epitope specificity was defined by stimulation with overlapping peptides, spanning the αs1-casein molecule. HLA restriction was determined in proliferation assays using antibodies blocking either HLA-DP, HLA-DQ or HLA-DR. HLA genotyping was performed in 32 subjects with CMA, 23 atopic and 22 non-atopic individuals. Results: Ten TCCs were restricted to HLA-DQ, 6 TCCs to HLA-DR and 4 TCCs to HLA-DP. The sequence in αs1-casein that was most immunogenic to T cells from children with CMA contained T cell epitopes restricted to DQB1*0201, DPB1*0401 and DRB1*1501. The DQB1*0501 allele frequency was lower in children with CMA than in non-atopic children, but this difference could not be confirmed in an additional group of subjects with and without CMA. Conclusions: HLA-DQ plays a substantial role in the presentation of T cell epitopes in αs1-casein. However, HLA class II allele frequencies do not show major differences between cow’s milk allergic, atopic and non-atopic subjects. T cell epitopes in the most immunogenic region are presented by various abundantly present HLA genotypes. Therefore, this sequence may be a suitable target for peptide immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of Human Leucocyte Antigen DQ in the Presentation of T Cell Epitopes in the Major Cow’s Milk Allergen αs1-Casein

Ruiter

Rozemuller²,

Dijk³

et al. 2007

Int Arch Allergy Immunol

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“…However, other studies have not demonstrated T cell cross-reactivity between allergens with a similar degree of sequence identity, as was the case for the major latex allergens, Hev b 1 and Hev b 3, despite 47% sequence identity [29]. In light of these studies, and given that single amino acid substitutions can lead to loss of T cell reactivity [30,31,32], it is likely that shared key amino acid motifs are more important for T cell cross-reactivity than whole epitope sequences.…”

Section: Discussionmentioning

confidence: 99%

Clinical Allergy to Hazelnut and Peanut: Identification of T Cell Cross-Reactive Allergens

Glaspole

León

Prickett

et al. 2011

Int Arch Allergy Immunol

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Background: Peanut and tree nut allergies are life-threatening conditions for many affected individuals worldwide. Currently there is no cure. While co-allergy to peanut and tree nuts is a common clinical observation, and IgE cross-reactivity between peanut and tree nuts is reported, T cell cross-reactivity is poorly defined. Methods: Hazelnut-specific T cell lines were established using peripheral blood mononuclear cells from 5 subjects with co-allergy to hazelnut and peanut. These lines were stimulated with hazelnut and peanut extracts and purified major peanut allergens, Ara h 1 and Ara h 2. Proliferation was determined by ³H-thymidine incorporation and secretion of key Th1 (IFN-γ) and Th2 (IL-5) cytokines analysed by ELISA. Results: Hazelnut-specific T cell lines from all 5 subjects proliferated upon stimulation with both hazelnut and peanut extracts and for 4 subjects, to Ara h 1 and/or Ara h 2. Proliferating cells were mainly CD4+ T cells and produced both IL-5 and IFN-γ in response to hazelnut and peanut stimulation. Mitogenicity of extracts and allergens was excluded by their lack of stimulation of house dust mite-specific T cells. Conclusion: Our finding that hazelnut and peanut co-allergy is associated with cross-reactive T cell responses, driven partly by cross-reactivity to the major peanut allergens Ara h 1 and Ara h 2, points to future development of allergen immunotherapy by targeting cross-reactive T cells.

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“…Das liegt teilweise daran, dass in den vergangenen fünfzehn Jahren der Schwerpunkt der Allergieforschung auf der Analyse von T-Zell Epitopen lag, den Erkennungsstellen für die T-Zellen des Immunsystems [4,5]. Wir messen hingegen der humoralen Immunantwort eine ebenso bedeutende Rolle in der allergischen Reaktion zu und glauben, dass die Allergen-B-Zell Epitope wesentlich für die Induktion und selektive Steuerung einer Immunantwort sind.…”

Section: Allergenmolekül: Struktur Als Voraussetzung Für Ige-bindungunclassified

From the allergen-recognition by antibodies to new therapeutic concepts

Hantusch

Jensen‐Jarolim

2008

Wien Med Wochenschr

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Cross-linking of IgE antibodies through allergens is a basic event in type I allergy and leads to the immediate release of mediators like histamine, responsible for allergic symptoms like rhino-conjunctivitis or asthma. Critical for the binding of allergens to IgE are the IgE-epitopes, which represent a congregation of several amino acid residues often derived from different regions of the allergen. By means of the mimotope-technology, we isolated peptides from phage libraries, which were able to structurally mimic IgE-epitopes of the plant allergens Bet v 1 (birch) and Phl p 5a (timothy grass). Hence, these are candidates for an epitope-specific immunotherapy. In this mode of immunotherapy, it is the aim to induce IgG antibodies directed exclusively against the IgE-epitopes of allergens without induction of anaphylactogenic IgG species, and without the risk of anaphylaxis through cross-linking of IgE. Immunizing mice, we applied the mimotopes displayed on bacteriophages as well as on alternative carrier systems to enhance their antigenicity. With these systems it was possible to elicit an allergen-specific immune response, which was also accompanied by the appropriate T-cell help. Mimotopes resemble a promising concept for an epitope-tailored immunotherapy of allergic patients.

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Highly heterogeneous Phl p 5-specific T cells from patients with allergic rhinitis differentially recognize recombinant Phl p 5 isoallergens☆☆☆

Cited by 23 publications

References 41 publications

Role of Human Leucocyte Antigen DQ in the Presentation of T Cell Epitopes in the Major Cow’s Milk Allergen αs1-Casein

Role of Human Leucocyte Antigen DQ in the Presentation of T Cell Epitopes in the Major Cow’s Milk Allergen αs1-Casein

Clinical Allergy to Hazelnut and Peanut: Identification of T Cell Cross-Reactive Allergens

From the allergen-recognition by antibodies to new therapeutic concepts

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