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J Immunol. 2015 Jul 1;195(1):307-16. doi: 10.4049/jimmunol.1402199. Epub 2015 May 29.

Structural Analysis of Der p 1-Antibody Complexes and Comparison with Complexes of Proteins or Peptides with Monoclonal Antibodies.

Author information

1
University of Virginia, Charlottesville, VA 22908; Adam Mickiewicz University, 61-712 Poznan, Poland;
2
Indoor Biotechnologies, Inc., Charlottesville, VA 22903; and.
3
University of South Carolina, Columbia, SC 29208.
4
University of Virginia, Charlottesville, VA 22908;
5
University of South Carolina, Columbia, SC 29208 chruszcz@mailbox.sc.edu.

Abstract

Der p 1 is a major allergen from the house dust mite, Dermatophagoides pteronyssinus, that belongs to the papain-like cysteine protease family. To investigate the antigenic determinants of Der p 1, we determined two crystal structures of Der p 1 in complex with the Fab fragments of mAbs 5H8 or 10B9. Epitopes for these two Der p 1-specific Abs are located in different, nonoverlapping parts of the Der p 1 molecule. Nevertheless, surface area and identity of the amino acid residues involved in hydrogen bonds between allergen and Ab are similar. The epitope for mAb 10B9 only showed a partial overlap with the previously reported epitope for mAb 4C1, a cross-reactive mAb that binds Der p 1 and its homolog Der f 1 from Dermatophagoides farinae. Upon binding to Der p 1, the Fab fragment of mAb 10B9 was found to form a very rare α helix in its third CDR of the H chain. To provide an overview of the surface properties of the interfaces formed by the complexes of Der p 1-10B9 and Der p 1-5H8, along with the complexes of 4C1 with Der p 1 and Der f 1, a broad analysis of the surfaces and hydrogen bonds of all complexes of Fab-protein or Fab-peptide was performed. This work provides detailed insight into the cross-reactive and specific allergen-Ab interactions in group 1 mite allergens. The surface data of Fab-protein and Fab-peptide interfaces can be used in the design of conformational epitopes with reduced Ab binding for immunotherapy.

PMID:
26026055
PMCID:
PMC4475478
DOI:
10.4049/jimmunol.1402199
[Indexed for MEDLINE]
Free PMC Article

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