Phl p 2: Difference between revisions
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==Phl p 2 and huMab2== | ==Phl p 2 and huMab2== | ||
Publication Abstract from PubMed | |||
We report the three-dimensional structure of the complex between the major respiratory grass pollen allergen Phl p 2 and its | |||
specific human IgE-derived Fab. The Phl p 2-specific human IgE Fab has been isolated from a combinatorial library constructed | |||
from lymphocytes of a pollen allergic patient. When the variable domains of the IgE Fab were grafted onto human IgG1, the | |||
resulting Ab (huMab2) inhibited strongly the binding of allergic patients’ IgE to Phl p 2 as well as allergen-induced basophil | |||
degranulation. Analysis of the binding of the allergen to the Ab by surface plasmon resonance yielded a very low dissociation | |||
constant (KD � 1.1 � 10�10 M), which is similar to that between IgE and Fc�RI. The structure of the Phl p 2/IgE Fab complex | |||
was determined by x-ray crystallography to 1.9 Å resolution revealing a conformational epitope (876 Å2) comprised of the planar | |||
surface of the four-stranded anti-parallel �-sheet of Phl p 2. The IgE-defined dominant epitope is discontinuous and formed by | |||
21 residues located mostly within the � strands. Of the 21 residues, 9 interact directly with 5 of the 6 CDRs (L1, L3, H1, H2, H3) | |||
of the IgE Fab predominantly by hydrogen bonding and van der Waals interactions. Our results indicate that IgE Abs recognize | |||
conformational epitopes with high affinity and provide a structural basis for the highly efficient effector cell activation by allergen/ | |||
IgE immune complexes. The Journal of Immunology, 2009, 182: 2141–2151. | |||
[[Image:Phlp2_huMab2_direct_contacts.jpg]] | [[Image:Phlp2_huMab2_direct_contacts.jpg]] | ||
<scene name='Phl_p_2/Cpk_colored/2'>direct contacts</scene> | <scene name='Phl_p_2/Cpk_colored/2'>direct contacts</scene> | ||