TY - JOUR
T1 - Dimerization of the major birch pollen allergen bet v 1 is important for its in vivo IgE-cross-linking potential in mice
AU - Schöll, Isabella
AU - Kalkura, Narayana
AU - Shedziankova, Yuliya
AU - Bergmann, Alexander
AU - Verdino, Petra
AU - Knittelfelder, Regina
AU - Kopp, Tamara
AU - Hantusch, Brigitte
AU - Betzel, Christian
AU - Dierks, Rarsten
AU - Scheiner, Otto
AU - Boltz-Nitulescu, George
AU - Keller, Walter
AU - Jensen-Jarolim, Erika
PY - 2005/11/15
Y1 - 2005/11/15
N2 - In type 1 allergy, the cross-linking of membrane IgE on B lymphocytes and of cytophilic IgE on effector cells by their respective allergens are key events. For cross-linking two IgE molecules, allergens need at least two epitopes. On large molecules, these could be different epitopes in a multivalent, or identical epitopes in a symmetrical, fashion. However, the availability of epitopes may be limited on small allergens such as Bet v 1, the major birch pollen allergen. The present work analyzes whether dimerization is required for the cross-linking capacity of this allergen. In immunoblots, murine monoclonal and polyclonal human Bet v 1-specific Abs detected, besides a Bet v 1 monomer of 17 kDa, a dimer of 34 kDa. In dynamic light scattering, Bet v 1 appeared as dimers and even multimers, but a single condition could be defined where it behaved exclusively nionomerically. Small-angle x-ray scattering of the monomeric and dimeric samples resulted in diagrams agreeing with the calculated models. Circular dichroism measurements indicated that the structure of Bet v 1 was preserved under nionomeric conditions. Skin tests in Bet v 1-allergic mice were positive with Bet v 1 dimer, but remained negative using the monomer. Furthermore, in contrast to dimeric Bet v 1, the monomer was less capable of activating murine memory B cells for IgE production in vivo. Our data indicate that the presentation of two identical epitopes by dimerized allergens is a precondition for cross-linking of IgE on mast cells and B lymphocytes.
AB - In type 1 allergy, the cross-linking of membrane IgE on B lymphocytes and of cytophilic IgE on effector cells by their respective allergens are key events. For cross-linking two IgE molecules, allergens need at least two epitopes. On large molecules, these could be different epitopes in a multivalent, or identical epitopes in a symmetrical, fashion. However, the availability of epitopes may be limited on small allergens such as Bet v 1, the major birch pollen allergen. The present work analyzes whether dimerization is required for the cross-linking capacity of this allergen. In immunoblots, murine monoclonal and polyclonal human Bet v 1-specific Abs detected, besides a Bet v 1 monomer of 17 kDa, a dimer of 34 kDa. In dynamic light scattering, Bet v 1 appeared as dimers and even multimers, but a single condition could be defined where it behaved exclusively nionomerically. Small-angle x-ray scattering of the monomeric and dimeric samples resulted in diagrams agreeing with the calculated models. Circular dichroism measurements indicated that the structure of Bet v 1 was preserved under nionomeric conditions. Skin tests in Bet v 1-allergic mice were positive with Bet v 1 dimer, but remained negative using the monomer. Furthermore, in contrast to dimeric Bet v 1, the monomer was less capable of activating murine memory B cells for IgE production in vivo. Our data indicate that the presentation of two identical epitopes by dimerized allergens is a precondition for cross-linking of IgE on mast cells and B lymphocytes.
UR - http://www.scopus.com/inward/record.url?scp=27744514242&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.175.10.6645
DO - 10.4049/jimmunol.175.10.6645
M3 - Article
C2 - 16272319
AN - SCOPUS:27744514242
SN - 0022-1767
VL - 175
SP - 6645
EP - 6650
JO - The Journal of Immunology
JF - The Journal of Immunology
IS - 10
ER -