Naturally processed T cell–activating peptides of the major birch pollen allergen

Mutschlechner, Sonja; Egger, Matthias; Briza, Peter; Wallner, Michael; Lackner, Peter; Karle, Anette; Vogt, Anne B.; Fischer, Gottfried; Bohle, Barbara; Ferreira, Fátima

doi:10.1016/j.jaci.2009.10.052

Cited by 51 publications

(62 citation statements)

References 38 publications

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“…Allergen components are recognized by T-cells through T-cell epitopes, which are restricted by the interaction between T-cell receptors and major histocompatibility complex II (MHC II) [16]. If the genetic backgrounds of T-cell receptor and MHC II are similar between the dogs, then allergen recognition in the dogs should also be similar.…”

Section: Discussionmentioning

confidence: 99%

Flow Cytometric Analysis of Lymphocyte Proliferative Responses to Food Allergens in Dogs with Food Allergy

Fujimura

Masuda

Hayashiya

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. Two different allergy tests, antigen-specific immunoglobulin E quantification (IgE test) and flow cytometric analysis of antigen-specific proliferation of peripheral lymphocytes (lymphocyte proliferation test), were performed to examine differences in allergic reactions to food allergens in dogs with food allergy (FA). Thirteen dogs were diagnosed as FA based on clinical findings and elimination diet trials. Seven dogs clinically diagnosed with canine atopic dermatitis (CAD) were used as a disease control group, and 5 healthy dogs were used as a negative control group. In the FA group, 19 and 33 allergen reactions were identified using the serum IgE test and the lymphocyte proliferation test, respectively. Likewise, in the CAD group, 12 and 6 allergen reactions and in the healthy dogs 3 and 0 allergen reactions were identified by each test, respectively. A significant difference was found between FA and healthy dogs in terms of positive allergen detection by the lymphocyte proliferation test, suggesting that the test can be useful to differentiate FA from healthy dogs but not from CAD. Both tests were repeated in 6 of the dogs with FA after a 1.5-to 5-month elimination diet trial. The IgE concentrations in 9 of 11 of the positive reactions decreased by 20-80%, whereas all the positive reactions in the lymphocyte proliferation test decreased to nearly zero (P<0.05), suggesting that lymphocytes against food allergens may be involved in the pathogenesis of canine FA.

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Section: Discussionmentioning

confidence: 99%

Flow Cytometric Analysis of Lymphocyte Proliferative Responses to Food Allergens in Dogs with Food Allergy

Fujimura

Masuda

Hayashiya

et al. 2011

The Journal of Veterinary Medical Science

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“…3A). This behavior is characteristic for immunogenic proteins 19 and again more similar to Bet v 1 18 than to Api g 1 which was degraded after 24 h (Fig. 3B).…”

Section: Discussionmentioning

confidence: 67%

“…In contrast, the α4β1‐integrin (very late antigen‐4) has been implicated in the recruitment of T cells to extraintestinal sites of inflammation, such as lungs and skin 17. We also determined T‐cell‐activating regions of Dau c 1 and subjected the protein to endolysosomal degradation as stability to lysosomal proteolysis has been considered a relevant factor for immunogenicity 18, 19. The resulting proteolytic fragments were sequenced by mass spectrometry and compared with the identified T‐cell‐activating regions.…”

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confidence: 99%

Characterization of the T-cell response to Dau c 1, the Bet v 1-homolog in carrot

Zulehner

Nagl

Briza

et al. 2016

Allergy

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BackgroundIn contrast to other Bet v 1‐related food allergens, the major carrot allergen, Dau c 1, has been suggested to induce food allergy independently from Bet v 1. As T cells are crucial in the sensitization process, we sought to characterize the T‐cell response to Dau c 1 and its cross‐reactivity with Bet v 1.MethodsDau c 1‐specific T‐cell lines (TCL) and clones (TCC) established from PBMC of birch pollen‐allergic patients with carrot allergy were analyzed for reactivity to Bet v 1, epitope specificity, allergen‐induced cytokine secretion, and expression of integrins α4β7 and α4β1, critical for gut and lung homing, respectively. mRNA expression of GATA3 and Tbet was analyzed in sorted CD3+ CD4+ CFSE low cells proliferating upon stimulation of PBMC with Dau c 1 or Bet v 1. Dau c 1 was incubated with endolysosomal proteases, and the resulting fragments were identified by mass spectrometry.ResultsAmong 14 distinct T‐cell‐activating regions, Dau c 1139–153 was recognized by 55% of the patients. Only 6 of 15 (40%) Dau c 1‐specific TCL and 9 of 21 (43%) TCC reacted with Bet v 1. Bet v 1‐nonreactive TCC were mainly Th1‐like and showed a higher expression of the integrin β7 and a significantly lower expression of the integrin β1 than Bet v 1‐positive TCC. A Th1‐like response was also detected in Dau c 1‐reactive CD3+ CD4+ CFSE low cells. Full‐length Dau c 1 was still detectable after 48 h of endolysosomal degradation. Proteolytic fragments of Dau c 1 matched its T‐cell‐activating regions.ConclusionDau c 1 displays several characteristics of sensitizing allergens, namely a major T‐cell‐activating region, low susceptibility to endolysosomal degradation, and induction of a Bet v 1‐independent T‐cell response. These cellular insights confirm that the major carrot allergen has a special status among Bet v 1‐related food allergens.

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“…To reveal the peptide sequences naturally presented by APCs and MHC class II molecules, the major birch pollen allergen Bet v 1 was digested by the endolysosomal extracts of dendritic cells (DCs) from four birch pollen allergy patients [43]. This resulted in the elution of 27 Bet v 1-derived peptides that were of 14-28 amino acids long.…”

Section: Mapping Of T Cell Epitopesmentioning

confidence: 99%

“…Data from proliferation and cytokine (IL-4 and IFN-γ) production demonstrated the presence of four T cell-recognizing regions on OVA. These T cell epitopes are each of 12 amino acids long and are found on OVA regions A39R50 (AMVYLGAKDSTR), S147R158 (SWVESQTNGIIR), K263E274 (KLTEWTSSNVME) and A329E340 (AAHAEINEAGRE) respectively.To reveal the peptide sequences naturally presented by APCs and MHC class II molecules, the major birch pollen allergen Bet v 1 was digested by the endolysosomal extracts of dendritic cells (DCs) from four birch pollen allergy patients [43]. This resulted in the elution of 27 Bet v 1-derived peptides that were of 14-28 amino acids long.…”

mentioning

confidence: 99%

From Molecule Studies of Allergens to Development of Immunotherapy of Allergies

Wai¹,

Leung²,

Chu³

et al. 2012

J Aller Ther

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IntroductionAllergy is a type I hypersensitivity disease prominently influences the quality of life. Allergens can strike one through the administration of drugs, insect sting, and ingestion of food or simply inhalation, making patients hard to strictly avoid these molecules. Allergen specific immunotherapy for grass pollen allergy has been put into clinical trials since 1950s and demonstrated satisfactory therapeutic effects [1]. It therefore paves the way for extensive researches on designing different allergen specific immunotherapy and unveiling the underlying mechanisms of these therapies.Defining the immunological mechanisms leading to allergy is crucial in designing allergen-specific immunotherapy. Sensitization of allergic individuals to allergens is initialized upon presentation of the allergen-derived peptides by the antigen presenting cells (APCs) through the major histocompatibility class II molecule (MHC class II) to naïve T cells, which are then activated and differentiated into type 2 T helper cells (Th2) (Figure 1). Cytokines such as IL-4 and IL-13 from Th2 cause a class switch in B cells to produce IgE antibodies specific to the particular allergen. When the individual is exposed to the same allergen again, IgE are massively produced, cross-link with the allergen and high affinity receptor (FcεRI) on mast cells and induce degranulation. Mediators such as histamine and leukotriene are released, resulting in inflammation and other associated anaphylactic responses [2].Molecular characteristics of allergens, in particular the identification of T cell and B cell epitopes, constitute important information for the design of therapeutic regimens. T cell epitopes refer to the short peptide fragments activating Th2 via MHC class II molecules while B cell epitopes, or IgE-binding epitopes, refer to the regions recognized by IgE on the allergen. With the identification of B cell epitopes at the molecular level, hypo-allergens possessing reduced allergenicity can be constructed through the introduction of point mutations on these IgE-binding regions [3,4]. The lack of IgE reactivity reduces the risk of these hypo-allergens to form cross-links with IgE and thus prevents the development of allergic side effects during treatment [5]. Meanwhile, since the T cell epitopes are conserved, these hypo-allergens are immunogenic and thus offer therapeutic effects. Alternatively, the employment of T cell epitopes in immunotherapy is believed to be a potential strategy since small peptide fragments are incapable to form cross-link with IgE but yet immunogenic to modulate immune responses [6]. AbstractAllergies are hypersensitive reactions that affect over 25% of the world population. Extensive studies have been directed to define patho-immunological mechanisms of allergy and the molecular characteristics of allergens. The emerging B cell and T cell epitope database has greatly facilitated the development of epitope-based immunotherapy that aims at modulating patients' immune responses towards a specific allergen. Modifi...

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Naturally processed T cell–activating peptides of the major birch pollen allergen

Cited by 51 publications

References 38 publications

Flow Cytometric Analysis of Lymphocyte Proliferative Responses to Food Allergens in Dogs with Food Allergy

Flow Cytometric Analysis of Lymphocyte Proliferative Responses to Food Allergens in Dogs with Food Allergy

Characterization of the T-cell response to Dau c 1, the Bet v 1-homolog in carrot

From Molecule Studies of Allergens to Development of Immunotherapy of Allergies

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