title: Antigenic Determinants of Der p 1: Specificity and Cross-Reactivity Associated with IgE Antibody Recognition.
abstract: Der p 1 and Der f 1 are major allergens from Dermatophagoides pteronyssinus and D. farinae, respectively. An analysis of antigenic determinants on both allergens was performed by site-directed mutagenesis. The analysis was based on the x-ray crystal structures of the allergens in complex with Fab fragments of three murine mAbs that interfere with IgE Ab binding: the two Der p 1-specific mAbs 5H8 and 10B9, and the cross-reactive mAb 4C1. On one hand, selected residues in the epitopes for mAb 5H8 and mAb 4C1 were substituted with amino acids that resulted in impaired Ab binding to Der p 1. On the other hand, an epitope for the Der p 1-specific mAb 10B9, which partially overlaps with mAb 4C1, was created in Der f 1. The mutation of 1-3 aa residues in Der f 1 was sufficient to bind mAb 10B9. These residues form hydrogen bonds with CDRs of the Ab other than H CDR3. This observation unveils an exception to the dominant role of H CDR3 commonly observed in Ag recognition. Overall, this study resulted in the identification of important residues for mAb and IgE Ab recognition in group 1 mite allergens. This information can be used to engineer allergen mutants with reduced IgE Ab binding for immunotherapy.
authors.affiliation: Indoor Biotechnologies Inc., Charlottesville, VA 22903.
authors.forename: Jill
authors.initials: J
authors.lastname: Glesner
authors.affiliation: Indoor Biotechnologies Inc., Charlottesville, VA 22903.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Vailes
authors.affiliation: University of South Carolina, Columbia, SC 29208; and.
authors.forename: Caleb
authors.initials: C
authors.lastname: Schlachter
authors.affiliation: University of South Carolina, Columbia, SC 29208; and.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Mank
authors.affiliation: University of Virginia, Charlottesville, VA 22908.
authors.forename: Wladek
authors.identifier: 0000-0001-7075-7090
authors.initials: W
authors.lastname: Minor
authors.affiliation: University of Virginia, Charlottesville, VA 22908.
authors.forename: Tomasz
authors.identifier: 0000-0001-9933-346X
authors.initials: T
authors.lastname: Osinski
authors.affiliation: University of South Carolina, Columbia, SC 29208; and.
authors.forename: Maksymilian
authors.identifier: 0000-0001-7521-5485
authors.initials: M
authors.lastname: Chruszcz
authors.affiliation: Indoor Biotechnologies Inc., Charlottesville, VA 22903.
authors.forename: Martin D
authors.identifier: 0000-0002-0845-3632
authors.initials: MD
authors.lastname: Chapman
authors.affiliation: Indoor Biotechnologies Inc., Charlottesville, VA 22903; apomes@inbio.com.
authors.forename: Anna
authors.identifier: 0000-0002-8729-1829
authors.initials: A
authors.lastname: Pomés
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000737:chemistry; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D060829:Arthropod Proteins / Q000276:immunology*; D001666:Binding Sites, Antibody; D003429:Cross Reactions; D003546:Cysteine Endopeptidases / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology*; D016297:Mutagenesis, Site-Directed
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D000939:Epitopes; D007073:Immunoglobulin E; D003546:Cysteine Endopeptidases; C451159:Dermatophagoides farinae antigen f 1; C451162:Dermatophagoides pteronyssinus antigen p 1