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| ==Phl p 2 and huMab2== | | ==Phl p 2 and huMab2== |
| Publication Abstract from PubMed
| | {{ABSTRACT_PMID_19201867}} |
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| We report the three-dimensional structure of the complex between the major respiratory grass pollen allergen Phl p 2 and its
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| specific human IgE-derived Fab. The Phl p 2-specific human IgE Fab has been isolated from a combinatorial library constructed
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| from lymphocytes of a pollen allergic patient. When the variable domains of the IgE Fab were grafted onto human IgG1, the
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| resulting Ab (huMab2) inhibited strongly the binding of allergic patients’ IgE to Phl p 2 as well as allergen-induced basophil
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| degranulation. Analysis of the binding of the allergen to the Ab by surface plasmon resonance yielded a very low dissociation
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| 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
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| was determined by x-ray crystallography to 1.9 Å resolution revealing a conformational epitope (876 Å2) comprised of the planar
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| surface of the four-stranded anti-parallel �-sheet of Phl p 2. The IgE-defined dominant epitope is discontinuous and formed by
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| 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)
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| of the IgE Fab predominantly by hydrogen bonding and van der Waals interactions. Our results indicate that IgE Abs recognize
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| conformational epitopes with high affinity and provide a structural basis for the highly efficient effector cell activation by allergen/IgE immune complexes. ''High-Affinity IgE Recognition of a Conformational Epitope of the Major Respiratory Allergen Phl p 2 As Revealed by X-Ray Crystallography'' by Sivaraman Padavattan,2* Sabine Flicker,2† Tilman Schirmer,* Christoph Madritsch,†
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| Stefanie Randow,‡ Gerald Reese,‡ Stefan Vieths,‡ Christian Lupinek,† Christof Ebner,§
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| Rudolf Valenta,3,4†¶ and Zora Markovic-Housley3*The Journal of Immunology, 2009, 182: 2141–2151.
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| [[Image:Phlp2_huMab2_direct_contacts.jpg]] | | [[Image:Phlp2_huMab2_direct_contacts.jpg]] |
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