Antigen presentation of the immunodominant T-cell epitope of the major mugwort pollen allergen, Art v 1, is associated with the expression of HLA-DRB1∗01

Jahn‐Schmid, Beatrice; Fischer, Gottfried; Bohle, Barbara; Faé, Ingrid; Gadermaier, Gabriele; Dedic, Azra; Ferreira, Fátima; Ebner, Christof

doi:10.1016/j.jaci.2004.10.010

Cited by 59 publications

(84 citation statements)

References 32 publications

(124 reference statements)

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“…Cutoff was defined as mean OD + 5 SD of values obtained with sera from five nonallergic individuals. OD ratios of Amb a 1/Art v 6 within 0.5 and 2.0 were interpreted as "comparable" IgE reactivity (patients 23-44); OD ratios $2 or #0.5 were interpreted as "preferential" recognition of Amb a 1 (patients [19][20][21][22] 3 for mugwort, respectively. All patients had recurrent rhinitis/conjunctivitis during late summer and positive skin prick tests to either ragweed or mugwort pollen or to both weeds.…”

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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

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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.

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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

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“…T cell lines (TCL) and T cell clones (TCC) were established as described previously from PBMC of mugwort-allergic individuals using purified nArt v 1 or rArt v 1 as initial stimulus (10,14). TCL or TCC (2 ϫ 10 4 ) were stimulated with allergen (10 g/ml) or peptides (5 g/ml, unless noted otherwise) presented by autologous PBMC or HLA-defined EBV-transformed B cell lines or HEK293 cells (human embryonic kidney epithelial cells) transfected with Ag-presenting molecules.…”

Section: Allergen-specific T Cellsmentioning

confidence: 99%

“…Molecules involved in HLA restriction were revealed by proliferation assays performed in the presence of blocking anti-HLA-DP, -DQ, or -DR Abs as described before (10,14). To study the capacity of different HLA-DR molecules to present Art v 1 [25][26][27][28][29][30][31][32][33][34][35][36] , peptide-specific TCC were stimulated with different, irradiated EBV-transformed B cells expressing defined HLA-DR-molecules (as listed in Fig.…”

Section: Hla-dr Crosspresentation Experimentsmentioning

confidence: 99%

“…However, in striking contrast to other allergens that contain multiple T cell epitopes (11)(12)(13), Art v 1 harbors only one single immunodominant epitope, Art v 1 [25][26][27][28][29][30][31][32][33][34][35][36] (KCIEWEKAQHGA), located in the defensin domain and recognized by 85% of Art v 1-reactive mugwort pollenallergic patients. The minimal epitope in Art v 1 [25][26][27][28][29][30][31][32][33][34][35][36] consists of 5-10 aa, and 3-5 aa within this core region have been shown to be relevant for T cell proliferation depending on the clonotypic TCR (14). The presentation of Art v 1 [25][26][27][28][29][30][31][32][33][34][35][36] has been shown to be HLA-DR-restricted (10,14).…”

mentioning

confidence: 99%

“…The minimal epitope in Art v 1 [25][26][27][28][29][30][31][32][33][34][35][36] consists of 5-10 aa, and 3-5 aa within this core region have been shown to be relevant for T cell proliferation depending on the clonotypic TCR (14). The presentation of Art v 1 [25][26][27][28][29][30][31][32][33][34][35][36] has been shown to be HLA-DR-restricted (10,14). Strikingly, recognition of Art v 1 [25][26][27][28][29][30][31][32][33][34][35][36] is highly associated with the HLA-DR1 phenotype ( p Ͻ 10 Ϫ6 ), which is expressed by ϳ70% of the patients.…”

mentioning

confidence: 99%

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Characterization of HLA Class II/Peptide-TCR Interactions of the Immunodominant T Cell Epitope in Art v 1, the Major Mugwort Pollen Allergen

Jahn‐Schmid

Sirven

Leb

et al. 2008

The Journal of Immunology

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More than 95% of mugwort pollen-allergic individuals are sensitized to Art v 1, the major allergen in mugwort pollen. Interestingly, the CD4 T cell response to Art v 1 involves only one single immunodominant peptide, Art v 125–36 (KCIEWEKAQHGA), and is highly associated with the expression of HLA-DR1. Therefore, we investigated the molecular basis of this unusual immunodominance among allergens. Using artificial APC expressing exclusively HLA-DRB1*0101 and HLA-DRA*0101, we formally showed that DR1 acts as restriction element for Art v 125–36-specific T cell responses. Further assessment of binding of Art v 125–36 to artificial HLA-DR molecules revealed that its affinity was high for HLA-DR1. Amino acid I27 was identified as anchor residue interacting with DR molecules in pocket P1. Additionally, Art v 125–36 bound with high affinity to HLA-DRB1*0301 and *0401, moderately to HLA-DRB1*1301 and HLA-DRB5*0101, and weakly to HLA-DRB1*1101 and *1501. T cell activation was also inducible by Art v 125–36-loaded, APC-expressing HLA molecules other than DR1, indicating degeneracy of peptide binding and promiscuity of TCR recognition. Specific binding of HLA-DRB1*0101 tetramers containing Art v 119–36 allowed the identification of Art v 125–36-specific T cells by flow cytometry. In summary, the immunodominance of Art v 125–36 relies on its affinity to DR1, but is not dictated by it. Future investigations at the molecular HLA/peptide/TCR and cellular level using mugwort pollen allergy as a disease model may allow new insights into tolerance and pathomechanisms operative in type I allergy, which may instigate new, T cell-directed strategies in specific immunotherapy.

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Marker Allergens of Weed Pollen: Basic Considerations and Diagnostic Benefits in Routine Clinical Practice

Gadermaier¹,

Stemeseder²,

Hemmer³

et al. 2017

Molecular Allergy Diagnostics

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Antigen presentation of the immunodominant T-cell epitope of the major mugwort pollen allergen, Art v 1, is associated with the expression of HLA-DRB1∗01

Cited by 59 publications

References 32 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

Characterization of HLA Class II/Peptide-TCR Interactions of the Immunodominant T Cell Epitope in Art v 1, the Major Mugwort Pollen Allergen

Marker Allergens of Weed Pollen: Basic Considerations and Diagnostic Benefits in Routine Clinical Practice

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