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 I 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-DRBI*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 inummodominant epitope. Conclusions: Allergy to Art v 1 is characterized by a uniform T-cell response. The disease is apparently associated with the HLA-DRI phenotype. Therefore, mugwort pollinosis is an ideal candidate for a peptide-based immunotherapy.