Basic and clinical immunology
Antigen presentation of the immunodominant T-cell epitope of the major mugwort pollen allergen, Art v 1, is associated with the expression of HLA-DRB101

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Background

Mugwort pollen allergens are the main cause of pollinosis in late summer in Europe. Ninety-five percent of patients allergic to mugwort are sensitized to the major allergen Art v 1. In contrast to other common pollen allergens that contain multiple T-cell epitopes, Art v 1 contains only 1 immunodominant T-cell epitope (Art v 125-36).

Objective

To characterize the minimal epitope of Art v 125-36 and to investigate a possible association of Art v 1 reactivity with HLA class II phenotypes.

Methods

Art v 1–specific T-cell lines and clones were established from 51 patients with clinically defined mugwort pollen allergy and IgE specific for Art v 1. To define minimal epitopes and binding sites within Art v 125-36, truncated and single-substitution analog peptides were used for T-cell stimulation. To study HLA restriction, monoclonal anti-HLA antibodies and antigen-presenting cells with defined HLA-DRB and -DQB1 alleles were used. HLA typing of patients with allergy was performed by hybridization with sequence-specific oligonucleotides, PCR, and nucleotide sequencing.

Results

In 96% of the patients, a cellular response to Art v 125-36 was obtained, and a core region of 5 to 10 amino acids containing 3 to 5 amino acids essential for T-cell reactivity was defined. The frequency of HLA-DRB101 in patients recognizing Art v 125-36 was significantly increased as compared with healthy controls (69% vs 21%; odds ratio, 8.45; P < 10−6), and HLA-DRB101 was identified as the main restriction element for the presentation of the immunodominant epitope.

Conclusions

Allergy to Art v 1 is characterized by a uniform T-cell response. The disease is apparently associated with the HLA-DR1 phenotype. Therefore, mugwort pollinosis is an ideal candidate for a peptide-based immunotherapy.

Section snippets

Characterization of patients allergic to mugwort

Fifty-one patients with mugwort pollen allergy (27 female and 24 male; mean age, 34.5 years; age range, 12-65 years) were included in this study. The diagnosis of mugwort allergy was based on typical clinical history, ie, recurrent rhinitis/conjunctivitis during late summer and positive skin prick tests (wheal diameter >5 mm) to mugwort pollen extract (ALK, Horsholm, Denmark). The CAP-RAST test for mugwort pollen (w6; Pharmacia Diagnostics, Uppsala, Sweden) was positive for all patients (mean

Immunodominance of Art v 125-36 in T-cell responses

All 51 patients included in this study had clinically defined mugwort pollen allergy and possessed serum IgE specific for nArt v 1 and rArt v 1, as determined by immunoblot and ELISA (not shown). In addition, nArt v 1 and rArt v 1 induced proliferation in PBMCs, oligoclonal TCLs, or TCCs derived from all patients. Similar proliferative responses were obtained in TCLs stimulated with nArt v 1, rArt v 1, and Art v 125-36 (mean ± SD: 41,066 ± 27,849 cpm, 44,104 ± 30,626 cpm, and 46,136 ± 30,626

Discussion

Mugwort pollen allergy is frequently encountered in Central Europe, and sensitization to the major allergen Art v 1 is observed in the vast majority of patients. Individuals allergic to mugwort who display IgE against Art v 1 also respond to the immunodominant peptide Art v 125-36 with their T cells and a typical TH2 response.11 In this study, the minimal epitope and essential amino acids within Art v 125-36 were characterized, and their restriction by HLA-DR was demonstrated. The T-cell

References (34)

  • F.T. Spieksma et al.

    City spore concentrations in the European Economic Community (EEC). IV. Summer weed pollen (Rumex, Plantago, Chenopodiaceae, Artemisia), 1976 and 1977

    Clin Allergy

    (1980)
  • F.G. Futin et al.

    Artemisia

    (1976)
  • B. Wuthrich et al.

    Celery allergy associated with birch and mugwort pollinosis

    Allergy

    (1990)
  • L. Bauer et al.

    IgE cross-reactivity between birch pollen, mugwort pollen and celery is due to at least three distinct cross-reacting allergens: immunoblot investigation of the birch-mugwort-celery syndrome

    Clin Exp Allergy

    (1996)
  • H. Breiteneder et al.

    Molecular characterization of Api g 1, the major allergen of celery (Apium graveolens), and its immunological and structural relationships to a group of 17-kDa tree pollen allergens

    Eur J Biochem

    (1995)
  • N. Wopfner et al.

    Molecular and immunological characterization of profilin from mugwort pollen

    Biol Chem

    (2002)
  • M. Himly et al.

    Art v 1, the major allergen of mugwort pollen, is a modular glycoprotein with a defensin-like and a hydroxyproline-rich domain

    FASEB J

    (2003)
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