title: Structural Analysis of Der p 1-Antibody Complexes and Comparison with Complexes of Proteins or Peptides with Monoclonal Antibodies.
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.
authors.affiliation: University of Virginia, Charlottesville, VA 22908; Adam Mickiewicz University, 61-712 Poznan, Poland;
authors.forename: Tomasz
authors.initials: T
authors.lastname: Osinski
authors.affiliation: Indoor Biotechnologies, Inc., Charlottesville, VA 22903; and.
authors.forename: Anna
authors.initials: A
authors.lastname: Pomés
authors.affiliation: University of Virginia, Charlottesville, VA 22908; Adam Mickiewicz University, 61-712 Poznan, Poland;
authors.forename: Karolina A
authors.initials: KA
authors.lastname: Majorek
authors.affiliation: Indoor Biotechnologies, Inc., Charlottesville, VA 22903; and.
authors.forename: Jill
authors.initials: J
authors.lastname: Glesner
authors.affiliation: University of South Carolina, Columbia, SC 29208.
authors.forename: Lesa R
authors.initials: LR
authors.lastname: Offermann
authors.affiliation: Indoor Biotechnologies, Inc., Charlottesville, VA 22903; and.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Vailes
authors.affiliation: Indoor Biotechnologies, Inc., Charlottesville, VA 22903; and.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Chapman
authors.affiliation: University of Virginia, Charlottesville, VA 22908;
authors.forename: Wladek
authors.initials: W
authors.lastname: Minor
authors.affiliation: University of South Carolina, Columbia, SC 29208 chruszcz@mailbox.sc.edu.
authors.forename: Maksymilian
authors.identifier: http://orcid.org/0000-0001-7521-5485
authors.initials: M
authors.lastname: Chruszcz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000276:immunology; D039741:Antigens, Dermatophagoides / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D060829:Arthropod Proteins / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D039981:Pyroglyphidae / Q000737:chemistry / Q000276:immunology; D016415:Sequence Alignment
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D003546:Cysteine Endopeptidases; C451159:Dermatophagoides farinae antigen f 1; C451162:Dermatophagoides pteronyssinus antigen p 1