Art v 1, the major allergen of mugwort pollen, is a modular glycoprotein with a defensin-like and a hydroxyproline-rich domain.
In late summer, pollen grains originating from Compositae weeds (e.g., mugwort, ragweed) are a major source of allergens worldwide. Here, we report the isolation of a cDNA clone coding for Art v 1, the major allergen of mugwort pollen. Sequence analysis showed that Art v 1 is a secreted allergen with an N-terminal cysteine-rich domain homologous to plant defensins and a C-terminal proline-rich region containing several (Ser/Ala)(Pro)2-4 repeats. Structural analysis showed that some of the proline residues in the C-terminal domain of Art v 1 are posttranslationally modified by hydroxylation and O-glycosylation. The O-glycans are composed of 3 galactoses and 9-16 arabinoses linked to a hydroxyproline and represent a new type of plant O-glycan. A 3-D structural model of Art v 1 was generated showing a characteristic "head and tail" structure. Evaluation of the antibody binding properties of natural and recombinant Art v 1 produced in Escherichia coli revealed the involvement of the defensin fold and posttranslational modifications in the formation of epitopes recognized by IgE antibodies from allergic patients. However, posttranslational modifications did not influence T-cell recognition. Thus, recombinant nonglycosylated Art v 1 is a good starting template for engineering hypoallergenic vaccines for weed-pollen therapy.
Himly
Martin
M
Institute of Genetics and General Biology, University of Salzburg, A-5020 Salzburg, Austria.
Jahn-Schmid
Beatrice
B
Dedic
Azra
A
Kelemen
Peter
P
Wopfner
Nicole
N
Altmann
Friedrich
F
van Ree
Ronald
R
Briza
Peter
P
Richter
Klaus
K
Ebner
Christof
C
Ferreira
Fátima
F
D000485:Allergens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D052179:Antigens, Plant; D019306:Artemisia / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D023082:Defensins / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D006909:Hydroxyproline / Q000737:chemistry; D007073:Immunoglobulin E / Q000276:immunology; D008958:Models, Molecular; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D011058:Pollen / Q000009:adverse effects; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000628:therapy; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens; D052179:Antigens, Plant; C102724:Art v 1 protein, mugwort; D023082:Defensins; D006023:Glycoproteins; D010940:Plant Proteins; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D006909:Hydroxyproline