Antigenic Determinants of Der p 1: Specificity and Cross-Reactivity Associated with IgE Antibody Recognition

• Published in: The Journal of immunology (1950) Vol. 198; no. 3; pp. 1334 - 1344
• Main Authors: Glesner, Jill, Vailes, Lisa D, Schlachter, Caleb, Mank, Nicholas, Minor, Wladek, Osinski, Tomasz, Chruszcz, Maksymilian, Chapman, Martin D, Pomés, Anna
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 01-02-2017
• Subjects: Allergens; Animals; Antibodies, Monoclonal - immunology; Antigen-Antibody Complex - chemistry; Antigenic determinants; Antigens, Dermatophagoides - immunology; Arthropod Proteins - immunology; Binding Sites, Antibody; Complementarity-determining region 3; Cross Reactions; Cross-reactivity; Cysteine Endopeptidases - immunology; Der f 1 antigen; Der p 1 antigen; Dermatophagoides pteronyssinus; Epitopes; Epitopes - immunology; Hydrogen bonding; Immunoglobulin E; Immunoglobulin E - immunology; Immunotherapy; Monoclonal antibodies; Mutagenesis, Site-Directed; Mutants; Residues; Site-directed mutagenesis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1600072

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.