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

Autor: Fatima Ferreira, Beatrice Jahn-Schmid, Christof Ebner, Gabriele Gadermaier, Ingrid Fae, Azra Dedic, Barbara Bohle, Gottfried Fischer
Rok vydání: 2005
Předmět:
Zdroj: Journal of Allergy and Clinical Immunology. 115:399-404
ISSN: 0091-6749
DOI: 10.1016/j.jaci.2004.10.010
Popis: 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 −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.
Databáze: OpenAIRE