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Epitope specificity determines cross-protection of a SIT-induced IgG(4) antibody
AuthorValenta, R. ; Flicker, S. ; Gould, H. J. ; Durham, S. R. ; Valent, P. ; Keller, W. ; Beavil, R. ; Villalba, M. ; Focke-Tejkl, M. ; Garmatiuk, T. ; Zieglmayer, P. ; Fauland, K. ; Blatt, K. ; Shamji, M. H. ; James, L. K. ; Gadermaier, E.
Published in
Allergy: European Journal of Allergy and Clinical Immunology, Hoboken, 2016, Vol. 71, Issue 1, page 36-46
PublishedHoboken : Wiley-Blackwell, 2016
Document typeJournal Article
Keywords (DE)calcium-binding protein / cross-reactivity / pollen allergen / recombinant allergen / sit-induced igg antibody / allergen-specific immunotherapy / birch-pollen / tree pollen / 3-dimensional structure / relevant allergens / pan-allergens / food allergy / che a-3 / profilin
Project-/ReportnumberF 4605-B28
URNurn:nbn:at:at-ubmuw:3-1473 Persistent Identifier (URN)
 The work is publicly available
Epitope specificity determines cross-protection of a SIT-induced IgG(4) antibody [0.85 mb]
Abstract (English)

Background: The calcium-binding 2EF-hand protein Phl p 7 from timothy grass pollen is a highly cross-reactive pollen pan-allergen that can induce severe clinical symptoms in allergic patients. Recently, a human monoclonal Phl p 7-specific IgG(4) antibody (mAb102.1F10) was isolated from a patient who had received grass pollen-specific immunotherapy (SIT). Methods: We studied epitope specificity, cross-reactivity, affinity and cross-protection of mAb102.1F10 towards homologous calcium-binding pollen allergens. Sequence comparisons and molecular modelling studies were performed with ClustalW and SPADE, respectively. Surface plasmon resonance measurements were made with purified recombinant allergens. Binding and cross-reactivity of patients' IgE and mAb102.1F10 to calcium-binding allergens and peptides thereof were studied with quantitative RAST-based methods, in ELISA, basophil activation and IgE-facilitated allergen presentation experiments. Results: Allergens from timothy grass (Phl p 7), alder (Aln g 4), birch (Bet v 4), turnip rape (Bra r 1), lamb's quarter (Che a 3) and olive (Ole e 3, Ole e 8) showed high sequence similarity and cross-reacted with allergic patients' IgE. mAb102.1F10 bound the C-terminal portion of Phl p 7 in a calcium-dependent manner. It cross-reacted with high affinity with Ole e 3, whereas binding and affinity to the other allergens were low. mAb102.1F10 showed limited cross-inhibition of patients' IgE binding and basophil activation. Sequence comparison and surface exposure calculations identified three amino acids likely to be responsible for limited cross-reactivity. Conclusions: Our results demonstrate that a small number of amino acid differences among cross-reactive allergens can reduce the affinity of binding by a SITinduced IgG and thus limit cross-protection.

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