Structural Analysis Reveals Molecular Basis for Interactions of Group 1 Allergens with Species Specific and Cross-Reactive Antibodies

In order to analyze the antigenic surface of Group 1 allergens we determined structures of complexes of Der f 1 or Der p 1 with monoclonal antibodies. Structures of these complexes provide detailed information about the molecular basis of murine IgG antibodies species specificity and cross-reactivity. This type of analysis may be used to localize IgE epitopes on Group 1 allergens. X-ray diffraction analysis was used to investigate the molecular structures of Der f 1:4C1, Der p 1:4C1, Der p 1:10B9 and Der p 1:5H8 complexes. Structural data revealed that the 4C1 epitope is common to both Der f 1 and Der p 1, and in both allergens the epitope is formed by the same amino acids. The structure of the Der p 1:10B9 complex shows that the epitopes for 4C1 and 10B9 partially overlap. The monoclonal antibody 5H8 binds to a different fragment of Der p 1 and the binding site for this antibody does not overlap with the 10B9 and 4C1 epitopes. Structural analysis of Group 1 allergens in complexes with different antibodies not only revealed the specific amino acid residues involved in cross-reactivity, but also explained why antibodies 10B9 and 5H8 are species specific. Results of the structural studies will be used for the design of experiments allowing for the identification of IgE binding epitopes.