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J Immunol. 2017 Feb 1;198(3):1334-1344. doi: 10.4049/jimmunol.1600072. Epub 2016 Dec 30.

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

Author information

1
Indoor Biotechnologies Inc., Charlottesville, VA 22903.
2
University of South Carolina, Columbia, SC 29208; and.
3
University of Virginia, Charlottesville, VA 22908.
4
Indoor Biotechnologies Inc., Charlottesville, VA 22903; apomes@inbio.com.

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.

PMID:
28039303
PMCID:
PMC5263215
DOI:
10.4049/jimmunol.1600072
[Indexed for MEDLINE]
Free PMC Article

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