Development of an in vitro system for the study of allergens and allergen-specific immunoglobulin E and immunoglobulin G: Fcepsilon receptor I supercross-linking is a possible new mechanism of immunoglobulin G-dependent enhancement of type I allergic reactions.
BACKGROUND
IgE-dependent activation of mast cells (MCs) is a key pathomechanism of type I allergies. In contrast, allergen-specific IgG Abs are thought to attenuate immediate allergic reactions by blocking IgE binding and by cross-linking the inhibitory Fcgamma receptor IIB on MCs.


OBJECTIVE
To establish a defined in vitro system using human MCs to study the biological activity of allergens and to investigate the role of allergen-specific IgE and IgG.


METHODS
Purified human intestinal MCs sensitized with different forms of specific IgE Abs were triggered by monomeric and oligomeric forms of recombinant Bet v 1, the major birch pollen allergen, in the presence or absence of allergen-specific IgG Abs. Results MCs sensitized with an anti-Bet v 1 IgE mAb or sera obtained from birch pollen allergic patients released histamine and sulphidoleukotrienes after exposure to oligomeric Bet v 1. Monomeric Bet v 1 provoked mediator release only in MCs sensitized with patients sera but not in MCs sensitized with anti-Bet v 1 IgE mAb. Interestingly, MC activation could be induced by supercross-linking of monomeric Bet v 1 bound to monovalent IgE on MCs with a secondary allergen-specific IgG pAb. By using IgG F(ab')2 fragments we provide evidence that this effect is not a result of IgG binding to Fcgamma receptors.


CONCLUSIONS
This assay represents a new tool for the in vitro study of MC activation in response to natural and genetically modified allergens. Fcepsilon receptor I supercross-linking by allergen-specific IgG Abs provides a possible new mechanism of IgG-dependent enhancement of type I allergic reactions.
Sellge
G
G
Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany.
Laffer
S
S
Mierke
C
C
Vrtala
S
S
Hoffmann
M W
MW
Klempnauer
J
J
Manns
M P
MP
Valenta
R
R
Bischoff
S C
SC
D000485:Allergens / Q000276:immunology*; D000918:Antibody Specificity; D052179:Antigens, Plant; D029662:Betula / Q000276:immunology; D002478:Cells, Cultured; D003429:Cross Reactions; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000276:immunology; D006632:Histamine / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007422:Intestines / Q000276:immunology; D015289:Leukotrienes / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D018832:Molecular Chaperones / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology; D011058:Pollen / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
D000485:Allergens; D052179:Antigens, Plant; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; D015289:Leukotrienes; D018832:Molecular Chaperones; D010940:Plant Proteins; D017455:Receptors, IgE; D011994:Recombinant Proteins; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E; D006632:Histamine