Molecular determinants of allergen-induced effector cell degranulation.
BACKGROUND
Allergen-induced effector cell degranulation is a key event in allergic inflammation and leads to early-phase symptoms, such as allergic rhinitis, conjunctivitis, urticaria, or bronchial asthma.


OBJECTIVE
We sought to study molecular determinants of effector cell degranulation using a monoclonal IgE antibody specific for a peptide epitope of one of the most important respiratory allergens, the major grass pollen allergen Phl p 1, as a model system.


METHODS
A hybridoma cell line producing a monoclonal IgE antibody against a Phl p 1-derived peptide, P1, was established by means of immunization of mice and used to sensitize rat basophil leukemia cells, which were exposed to P1 monomer, P1 dimer, and P1 polymer.


RESULTS
It is demonstrated that the number of IgE epitopes on an allergen molecule and the concentration of allergen-specific IgE antibodies determine the extent of degranulation. The P1 monomer did not cause mediator release and prevented degranulation induced by polymeric P1.


CONCLUSIONS
Our results suggest that the number of IgE epitopes on an allergen molecule determines its allergenic activity and explains why increases of allergen-specific IgE levels make patients more sensitive to allergens. Allergen-derived monomeric structures isolated by means of combinatorial chemistry might be used to develop new therapeutic strategies for allergy.


CONCLUSIONS
Our study reveals molecular factors that determine the immediate allergenic activity of allergens and hence influence clinical sensitivity to these allergens.
Gieras
Anna
A
Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.
Focke-Tejkl
Margarete
M
Ball
Tanja
T
Verdino
Petra
P
Hartl
Arnulf
A
Thalhamer
Josef
J
Valenta
Rudolf
R
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015550:Cell Degranulation; D045744:Cell Line, Tumor; D000939:Epitopes; D007073:Immunoglobulin E / Q000276:immunology*; D015471:Leukemia, Basophilic, Acute / Q000276:immunology; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000276:immunology*; D051381:Rats
D000485:Allergens; D000911:Antibodies, Monoclonal; D000939:Epitopes; D010940:Plant Proteins; C090396:PHLPI protein, Phleum pratense; D007073:Immunoglobulin E