title: Suppression of allergen-specific B lymphocytes by chimeric protein-engineered antibodies.
abstract: House dust mites Dermatophagoides pteronyssinus (Dpt) are among the most frequent causes of allergy symptoms in Europe. Der p 1 is one of the major allergenic compounds of Dpt and the pathological Der p 1-specific B cells play a key role as producers of allergen-binding antibodies. The selective elimination of these cells by artificial protein molecules which inhibit the production of Dpt-recognizing IgE antibodies is a perspective therapeutic goal of allergy. A protein engineered chimeric molecule has been constructed, which binds Der p 1-specific B cells via their BCR and suppresses selectively the production of anti-Der p 1 antibodies via CR1. The synthetic peptide Der p 1 p52-71 and an anti-CD35 monoclonal antibody were used for the construction of Der p 1 chimera. The functional effects of engineered antibodies were analyzed in vitro using PBMCs from allergy patients. Significant inhibition of allergen-specific proliferation and reduction of Der p 1-IgE antibody production were observed after treatment of PBMCs from allergic patients with Der p 1-peptide chimera. Culturing of these PBMCs in the presence of the chimeric molecule increased the percentage of apoptotic (Annexin V-positive) B lymphocytes, but not T lymphocytes.
authors.affiliation: The Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
authors.forename: Nikola
authors.initials: N
authors.lastname: Kerekov
authors.forename: Antoaneta
authors.initials: A
authors.lastname: Michova
authors.forename: Maryia
authors.initials: M
authors.lastname: Muhtarova
authors.forename: Georgi
authors.initials: G
authors.lastname: Nikolov
authors.forename: Nikolina
authors.initials: N
authors.lastname: Mihaylova
authors.forename: Bogdan
authors.initials: B
authors.lastname: Petrunov
authors.forename: Maria
authors.initials: M
authors.lastname: Nikolova
authors.forename: Andrey
authors.initials: A
authors.lastname: Tchorbanov
mesh_terms: D000328:Adult; D000485:Allergens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D039741:Antigens, Dermatophagoides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D060829:Arthropod Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D015202:Protein Engineering / Q000379:methods; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1
keywords: 1-ethyl-3(3′-dimethylaminopropyl; 5-bromo-4-chloro-3-indolyl phosphate; Allergen-specific B lymphocytes; Allergy; B cell receptor; BCIP; BCR; CR1; Dermatophagoides pteronyssinus; Dpt; EDC; ELISA; ELISpot; FACS; FCS; FITC; HDM; IFN-γ; NBT; PBMCs; PE; Protein chimera; SCID; SD; SDS-PAGE; SIT; SLE; complement receptor 1; double stranded DNA; dsDNA; enzyme-linked immuno-sorbent analysis; enzyme-linked immunosorbent spot; fetal calf serum; fluorescein isothiocyanate; fluorescence-activated cell sorting; house dust mite; interferon gamma; mAb; monoclonal antibody; nitro blue tetrazolium; peripheral blood mononuclear cells; phicoerythrin; scFv; severe combined immunodeficiency; single chain Fv; sodium dodecyl sulfate-polyacrylamide gel electrophoresis; specific immunotherapy; standard deviation; systemic lupus erythematosus