TY - JOUR
T1 - Structural analysis of der p 1-antibody complexes and comparison with complexes of proteins or peptides with monoclonal antibodies
AU - Osinski, Tomasz
AU - Pomés, Anna
AU - Majorek, Karolina A.
AU - Glesner, Jill
AU - Offermann, Lesa R.
AU - Vailes, Lisa D.
AU - Chapman, Martin D.
AU - Minor, Wladek
AU - Chruszcz, Maksymilian
N1 - Publisher Copyright:
© 2015 by The American Association of Immunologists, Inc.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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 a 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.
AB - 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 a 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.
UR - http://www.scopus.com/inward/record.url?scp=84932090487&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1402199
DO - 10.4049/jimmunol.1402199
M3 - Article
C2 - 26026055
AN - SCOPUS:84932090487
SN - 0022-1767
VL - 195
SP - 307
EP - 316
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -