Open AccessA Phl p 7‐specific IgG4 antibody inhibits allergic patients IgE cross‐reactivity to allergens from the EF‐hand family: importance of affinity and degree of cross‐reactivity
Author(s) -
Gadermaier Elisabeth,
James Louise K,
Shamji Mohamed H,
Blatt Katrina,
Garmatiuk Tetiana,
Beavil Rebecca,
Flicker Sabine,
Valent Peter,
Durham Stephen R,
Gould Hannah J,
Valenta Rudolf
Publication year - 2014
Publication title -
clinical and translational allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.979
H-Index - 37
ISSN - 2045-7022
DOI - 10.1186/2045-7022-4-s2-o8
Subject(s) - medicine , cross reactivity , immunoglobulin e , immunology , reactivity (psychology) , allergy , cross reactions , antibody , pathology , alternative medicine
Methods and results Sequence comparison showed a comparable sequence identity of approximately 70% between the 2EF-hand pollen allergens (Timothy grass: Phl p 7; Alder: Aln g 4; Birch: Bet v 4; Turnip rape: Bra r 1; Lamb s quarter: Che a 3; Olive: Ole e 3) and a lower sequence identity of 44% with the 4EF-hand allergen from olive pollen (Ole e 8). While patients IgE showed extensive cross-reactivity with the EF-hand allergens, the Phl p 7-specific IgG4 showed limited cross-reactivity. Best cross-reactivity was observed with Ole e 3 whereas the other EF-hand allergens were less recognized by the Phl p 7-specific IgG4 in dot blot experiments. Calcium-depletion experiments showed that the binding of the Phl p 7-specific IgG4 depended on the presence of calcium. Using peptidespecific antisera the binding site of the IgG4 was located in the C-terminal portion of the allergen which contains the second calcium-binding EF-hand motif. Biacore experiments revealed interesting differences regarding the affinity of the Phl p 7-specific IgG4. Phl p 7 and Ole e 3 were recognized with the highest affinity (KD s: Phl p 7: 2,11x10-9M; Ole e 3: 6,18x10-9M) whereas the affinities to the other cross-reactive allergens was much lower (Bet v 4: 6,26x10-6M; Bra r 1: 6,57x10-6M; Aln g 4: 7,93x10-6M). The cross-inhibition of patients IgE reactivity to the EF-hand allergens and the inhibition of allergen-induced basophil activation obtained with the Phl p 7-specific IgG4 followed its intensity of cross-reactivity and affinity with the homologous allergens.