The T cell response to Art v 1, the major mugwort pollen allergen, is dominated by one epitope.
Mugwort (Artemisia vulgaris) pollen allergens represent the main cause of pollinosis in late summer in Europe. At least 95% of sera from mugwort pollen-allergic patients contain IgE against a highly glycosylated 24- to 28-kDa glycoprotein. Recently, this major allergen, termed Art v 1, was characterized, cloned in Escherichia coli, and produced in recombinant form. In the present study we characterized and compared the T cell responses to natural (nArt v 1) and recombinant Art v 1 (rArt v 1). In vitro T cell responses to nArt v 1 and rArt v 1 were studied in PBMC, T cell lines (TCL), and T cell clones (TCC) established from PBMC of mugwort-allergic patients. Stimulation of PBMC or allergen-specific TCL with either nArt v 1 or rArt v 1 resulted in comparable proliferative T cell responses. Eighty-five percent of the TCC reactive with rArt v 1 cross-reacted with the natural protein. The majority of the CD4(+)CD8(-)TCR alphabeta(+) Art v 1-specific TCC, obtained from 10 different donors, belonged to the Th2 phenotype. Epitope mapping of TCL and TCC using overlapping peptides revealed a single immunodominant T cell epitope recognized by 81% of the patients. Inhibition experiments demonstrated that the presentation of this peptide is restricted by HLA-DR molecules. In conclusion, the T cell response to Art v 1 is characterized by one strong immunodominant epitope and evidently differs from the T cell responses to other common pollen allergens known to contain multiple T cell epitopes. Therefore, mugwort allergy may be an ideal candidate for a peptide-based immunotherapy approach.
Jahn-Schmid
Beatrice
B
Department of Pathophysiology, Division of Immunopathology, University of Vienna, AKH-3Q, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Kelemen
Peter
P
Himly
Martin
M
Bohle
Barbara
B
Fischer
Gottfried
G
Ferreira
Fatima
F
Ebner
Christof
C
D000485:Allergens / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D052179:Antigens, Plant; D019306:Artemisia / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006683:HLA-DQ Antigens / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D006650:Histocompatibility Testing; D006801:Humans; D015151:Immunoblotting; D016056:Immunodominant Epitopes / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D010940:Plant Proteins / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D011058:Pollen / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*
D000485:Allergens; D052179:Antigens, Plant; C102724:Art v 1 protein, mugwort; D018984:Epitopes, T-Lymphocyte; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D016056:Immunodominant Epitopes; D010940:Plant Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D007073:Immunoglobulin E