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

Abstract

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.

Molecular Recognition Profiles and Clinical Patterns of PR-10 Sensitization in a Birch-Free Mediterranean Area

“…Since those molecules are not present on the chip, we can speculate that more Fagales pollen allergens could be useful for a more accurate diagnostic workup, especially in birch-free areas. In effect, it has been demonstrated that Dau c 1 from carrot [22] and Cor a 1 from hazelnut can sensitize patients in the absence of Bet v 1 sensitization [21]; thus, it is also possible to hypothesize that other PR-10s are able to act as primary sensitizers in areas such as the Mediterranean, where birch pollen levels are low or absent [6]. …”

Hydrolyzed diets may stimulate food-reactive lymphocytes in dogs

“…Third, since the protein sources in the hydrolyzed diets examined in this study were poultryfeather meal (D-1), and chicken meat (D-2) [2], they may have included T-cell epitopes taxonomically similar to many poultry proteins. In general, T-cell epitopes are conserved among major allergens with taxonomic similarity [28], and cross-reactivity against multiple allergens can occur [9,23,31]. T-cell epitopes should be conserved in poultry-related allergens; this may explain the "bird-egg syndrome" phenomenon of human allergic reactions to some avian meats [13] and feathers [27].…”

“…In a recent study, the major allergens from Japanese cedar and cypress Cry j 1 and Cha o 1, contained AA sequences with approximately 80% homology [26], and also contained identical T-cell epitope sequences recognized by human T-lymphocytes reactive to both Cry j 1 and Cha o 1 [23]. The Cry j 1 and Cha o 1 T-cell epitopes were also identical to various tree pollen and vegetable species epitopes [9,31]. Alpha-parvalbumin, a major allergen from chicken meat, contains AA sequences that are highly conserved (greater than 80% homology) in poultry and livestock animals, and in a previous study resulted in induction of cross-reactive human IgE [15].…”

Dendritic Cells and Their Role in Allergy: Uptake, Proteolytic Processing and Presentation of Allergens

“…A similar observation was found for the birch pollen (Bet v 1) homologues from food sources. Dau c 1 from carrot showed remarkable stability as compared to Api g 1 from celery [ 75 ].…”