title: Therapeutic targets for olive pollen allergy defined by gene markers modulated by Ole e 1-derived peptides.
abstract: Two regions of Ole e 1, the major olive-pollen allergen, have been characterized as T-cell epitopes, one as immunodominant region (aa91-130) and the other, as mainly recognized by non-allergic subjects (aa10-31). This report tries to characterize the specific relevance of these epitopes in the allergic response to olive pollen by analyzing the secreted cytokines and the gene expression profiles induced after specific stimulation of peripheral blood mononuclear cells (PBMCs). PBMCs from olive pollen-allergic and non-allergic control subjects were stimulated with olive-pollen extract and Ole e 1 dodecapeptides containing relevant T-cell epitopes. Levels of cytokines were measured in cellular supernatants and gene expression was determined by microarrays, on the RNAs extracted from PBMCs. One hundred eighty-nine differential genes (fold change >2 or <-2, P<0.05) were validated by qRT-PCR in a large population. It was not possible to define a pattern of response according the overall cytokine results but interesting differences were observed, mainly in the regulatory cytokines. Principal component (PCA) gene-expression analysis defined clusters that correlated with the experimental conditions in the group of allergic subjects. Gene expression and functional analyses revealed differential genes and pathways among the experimental conditions. A set of 51 genes (many essential to T-cell tolerance and homeostasis) correlated with the response to aa10-31 of Ole e 1. In conclusion, two peptides derived from Ole e 1 could regulate the immune response in allergic patients, by gene-expression modification of several regulation-related genes. These results open new research ways to the regulation of allergy by Oleaceae family members.
authors.affiliation: Immunology Department, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Calzada
authors.affiliation: Immunology Department, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Aguerri
authors.affiliation: Immunology Department, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain.
authors.forename: Selene
authors.initials: S
authors.lastname: Baos
authors.affiliation: Functional Genomics Unit Bioinformatics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Montaner
authors.affiliation: Genomics Department, Fundación de Investigación, Hospital General Universitario, Valencia, Spain; CIBERES, CIBER de Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mata
authors.affiliation: Functional Genomics Unit Bioinformatics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Allergy Department, Hospital Universitario Vírgen del Rocío, Sevilla, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Quiralte
authors.affiliation: Allergy Department, Hospital Universitario San Cecilio, Granada, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Florido
authors.affiliation: Immunology Department, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain; CIBERES, CIBER de Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lahoz
authors.affiliation: Immunology Department, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain; CIBERES, CIBER de Enfermedades Respiratorias, Madrid, Spain. Electronic address: bcardaba@fjd.es.
authors.forename: Blanca
authors.initials: B
authors.lastname: Cárdaba
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D052179:Antigens, Plant / Q000276:immunology* / Q000494:pharmacology; D016022:Case-Control Studies; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D005810:Multigene Family; D031658:Olea / Q000737:chemistry / Q000276:immunology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology; D010940:Plant Proteins / Q000276:immunology* / Q000494:pharmacology; D011058:Pollen / Q000737:chemistry / Q000276:immunology*; D061251:Primary Cell Culture; D025341:Principal Component Analysis; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood / Q000276:immunology* / Q000503:physiopathology
chemical_list: D052179:Antigens, Plant; D018984:Epitopes, T-Lymphocyte; D005819:Genetic Markers; C081946:Ole e I protein, Olea europaea; D009842:Oligopeptides; D010940:Plant Proteins; D007073:Immunoglobulin E
keywords: Gene-expression and allergy; Immunoregulatory response; Olive-pollen allergy; Peptide immunotherapy; Therapeutic gene targets