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.
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 1 25-36 ).


OBJECTIVE
To characterize the minimal epitope of Art v 1 25-36 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 1 25-36 , 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 1 25-36 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-DRB1 * 01 in patients recognizing Art v 1 25-36 was significantly increased as compared with healthy controls (69% vs 21%; odds ratio, 8.45; P < 10 -6 ), and HLA-DRB1 * 01 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.
Jahn-Schmid
Beatrice
B
Department of Pathophysiology, Medical University of Vienna, Vienna, Austria. beatrice.jahn-schmid@meduniwien.ac.at
Fischer
Gottfried F
GF
Bohle
Barbara
B
Faé
Ingrid
I
Gadermaier
Gabriele
G
Dedic
Azra
A
Ferreira
Fatima
F
Ebner
Christof
C
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology*; D052179:Antigens, Plant; D016022:Case-Control Studies; D002455:Cell Division; D002648:Child; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010940:Plant Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D000485:Allergens; D052179:Antigens, Plant; C102724:Art v 1 protein, mugwort; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C497841:HLA-DRB1*01 antigen; D016056:Immunodominant Epitopes; D010940:Plant Proteins