Bet v 1142-156 is the dominant T-cell epitope of the major birch pollen allergen and important for cross-reactivity with Bet v 1–related food allergens

Jahn‐Schmid, Beatrice; Radakovics, Astrid; Lüttkopf, D.; Scheurer, Stephan; Vieths, Stefan; Ebner, Christof; Bohle, Barbara

doi:10.1016/j.jaci.2005.04.019

Cited by 153 publications

(209 citation statements)

References 40 publications

Supporting

Mentioning

194

Contrasting

Unclassified

Order By: Relevance

“…3, Tables II, III). This finding was unexpected, because, for example, the food allergens homologous to the major birch pollen allergen, Bet v 1, all possess multiple epitope regions similar to Bet v 1 (24,25), and T cell cross stimulation has been observed for epitopes with 60-80% amino acid similarity and 40-67% amino acid identity (26). For Amb a 1, we have previously found .20 distinct T cell epitope regions, including 3 dominant epitopes (Amb a 1 178-189 , Amb a 1 199-216 , and Amb a 1 343-357 ) recognized by .45%, and 7 epitopes recognized by .25% of patients (22).…”

Section: Discussionmentioning

confidence: 99%

Humoral and Cellular Cross-Reactivity between Amb a 1, the Major Ragweed Pollen Allergen, and Its Mugwort Homolog Art v 6

Jahn‐Schmid

Hauser

Wopfner

et al. 2012

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Ragweed and mugwort are closely related weeds that represent the major cause of pollen allergy in late summer. Concomitant sensitization and clinical cross-reactivity frequently occur in subjects who are coexposed to both pollen species, and have implications for diagnosis and specific immunotherapy. Molecules involved in this cross-reactivity might be Amb a 1, the major ragweed pollen allergen, and Art v 6, a highly homologous allergen from mugwort. Therefore, we investigated the IgE and T cell response to Art v 6 of 60 weed pollen-allergic patients and assessed its immunological cross-reactivity with Amb a 1. Results of ELISA inhibition experiments suggested that both allergens are largely cross-reactive, but Amb a 1 possesses more IgE epitopes than Art v 6. In patients with IgE to both allergens, Amb a 1-induced T cell lines and clones responded weakly to Art v 6. Moreover, Art v 6-induced T cell lines responded stronger to Amb a 1. T cell epitope mapping of Art v 6 revealed that it contains only a few cross-reactive epitopes, which is opposed to the multiple T cell-activating regions present in Amb a 1. In summary, Amb a 1 can elicit more diverse allergen-specific IgE and T cell responses than Art v 6 and dominates the cross-reactivity with its homolog. Nevertheless, Art v 6 can act as a primary sensitizing allergen in areas with high mugwort pollen exposure, and consequently may facilitate sensitization to Amb a 1 by epitope cross-recognition of T and B cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Humoral and Cellular Cross-Reactivity between Amb a 1, the Major Ragweed Pollen Allergen, and Its Mugwort Homolog Art v 6

Jahn‐Schmid

Hauser

Wopfner

et al. 2012

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cytokine secretion was determined in culture supernatants harvested 48 h after stimulation of the TCC with 5 g/ml Bet v 1 and autologous irradiated PBMC, using an ELISA with Endogen Matched Ab Pairs (Endogen) according to the manufacturer's instructions. Limits of detection were: IL-4, 9 pg/ml; IFN-␥, 9.5 pg/ml; IL-10, 4.7 pg/ml) (31). TCC were assigned to Th subsets as follows: Th2, ratio IL-4/IFN-␥ of Ͼ5; Th1, ratio IFN-␥/IL-4 of Ͼ5; and Th0, ratio IFN-␥/IL-4 between 0.2 and 5.…”

Section: Generation Of T Cell Clones (Tcc)mentioning

confidence: 98%

Assessment of Bet v 1-Specific CD4+ T Cell Responses in Allergic and Nonallergic Individuals Using MHC Class II Peptide Tetramers

Overtvelt

Wambre

Maillère

et al. 2008

The Journal of Immunology

Self Cite

112

118

View full text Add to dashboard Cite

In this study, we used HLA-DRB1*0101, DRB1*0401, and DRB1*1501 peptide tetramers combined with cytokine surface capture assays to characterize CD4+ T cell responses against the immunodominant T cell epitope (peptide 141–155) from the major birch pollen allergen Bet v 1, in both healthy and allergic individuals. We could detect Bet v 1-specific T cells in the PBMC of 20 birch pollen allergic patients, but also in 9 of 9 healthy individuals tested. Analysis at a single-cell level revealed that allergen-specific CD4+ T cells from healthy individuals secrete IFN-γ and IL-10 in response to the allergen, whereas cells from allergic patients are bona fide Th2 cells (producing mostly IL-5, some IL-10, but no IFN-γ), as corroborated by patterns of cytokines produced by T cell clones. A fraction of Bet v 1-specific cells isolated from healthy, but not allergic, individuals also expresses CTLA-4, glucocorticoid-induced TNF receptor, and Foxp 3, indicating that they represent regulatory T cells. In this model of seasonal exposure to allergen, we also demonstrate the tremendous dynamics of T cell responses in both allergic and nonallergic individuals during the peak pollen season, with an expansion of Bet v 1-specific precursors from 10−6 to 10−3 among circulating CD4+ T lymphocytes. Allergy vaccines should be designed to recapitulate such naturally protective Th1/regulatory T cell responses observed in healthy individuals.

show abstract

“…Carrot allergy is generally considered a birch pollen‐related food allergy with Dau c 1 as major allergen 2. Birch pollen‐related food allergy results from primary sensitization to the major birch pollen allergen followed by cross‐reactivity of Bet v 1‐specific IgE antibodies and T cells with Bet v 1‐related food proteins 3, 4, 5, 6. Consequently, Bet v 1 and homologous food allergens are usually not considered to show sensitizing activity.…”

mentioning

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

View full text Add to dashboard Cite

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.

show abstract

Bet v 1142-156 is the dominant T-cell epitope of the major birch pollen allergen and important for cross-reactivity with Bet v 1–related food allergens

Cited by 153 publications

References 40 publications

Humoral and Cellular Cross-Reactivity between Amb a 1, the Major Ragweed Pollen Allergen, and Its Mugwort Homolog Art v 6

Humoral and Cellular Cross-Reactivity between Amb a 1, the Major Ragweed Pollen Allergen, and Its Mugwort Homolog Art v 6

Assessment of Bet v 1-Specific CD4+ T Cell Responses in Allergic and Nonallergic Individuals Using MHC Class II Peptide Tetramers

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

Contact Info

Product

Resources

About