[The high-affinity IgE receptor: lessons from structural analysis].
The high affinity receptor for IgE, FcERI, is at the core of the allergic reaction. This receptor is expressed mainly on mast cells and basophils. Interaction of an allergen with its specific IgE bound to FcERI triggers cell activation, which induces the release of numerous mediators that are responsible for allergic manifestations. The recent increase in the prevalence of allergic diseases in developed countries has resulted in renewed efforts towards the development of new drugs. One of these is a humanised antibody directed against the IgE ligand. This antibody recognises specifically free but not FcERI-bound IgE thus preventing ligand binding and subsequent cell activation. This antibody has shown some efficacy in clinical trials involving patients with asthma and allergic rhinitis. The recent elucidation of the tridimensional structure of the complex between IgE and FcERI provides unexpected information regarding the mechanism of assembly of the complex, which now can be used to design small chemical compounds capable of specifically inhibiting this interaction.
Blank
Ulrich
U
Institut Pasteur, Unité d'Immuno-Allergie, 25, rue du Docteur Roux, 75724 Paris, France. ublank@pasteur.fr
Jouvin
Marie-Hélène
MH
Guérin-Marchand
Claudine
C
Kinet
Jean-Pierre
JP
D020816:Amino Acid Motifs; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000627:therapeutic use; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000628:therapy; D001491:Basophils / Q000276:immunology; D002986:Clinical Trials as Topic; D015195:Drug Design; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D046911:Macromolecular Substances; D008407:Mast Cells / Q000276:immunology; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017455:Receptors, IgE / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D017452:Receptors, IgG / Q000737:chemistry / Q000276:immunology; D013329:Structure-Activity Relationship
D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D046911:Macromolecular Substances; D017455:Receptors, IgE; D017452:Receptors, IgG; C026408:anti-IgE antibodies; D007073:Immunoglobulin E