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The Immunogenetics of Allergic Sensitization: Selection of the IgE Repertoire $0.00
Authors:  Michael Zemlin, Tobias Rogosch, Sebastian Kerzel, University Children's Hospital, Marburg, Germany, and others
Abstract:
The central effector molecule of allergic immune responses is immunoglobulin E (IgE). IgE bound to the surface of mast cells generates the interface between allergens and the immune system on the effector side of the allergic immune response. The cross-linkage of two adjacent membrane bound IgE molecules is the most important trigger for mast cell degranulation, leading to the consecutive release of proinflammatory mediators that orchestrate the allergic inflammation.
The functional properties of the interface between the allergen and the immune system are an interesting target for understanding the mechanisms of allergic sensitization and the allergic immune response. The core of this interface is the classical antigen binding site, which is the part of the immunoglobulin that determines the specificity and affinity of the antibody. The almost infinite diversity of the antibody is generated by the processes of combinatorial diversity, junctional diversity, and somatic point mutations. Thus, during allergic sensitization, the antibody repertoire is focused by selection processes, leading to expansion of specific B cell clones.
Studies of the IgE repertoire have started only recently due to the availability of novel RT-PCR based techniques. Initial studies suggested that the IgE repertoire may be differently regulated than the repertoires of other isotypes. Particularly in allergic patients, the repertoire of IgE heavy chain transcripts displayed remarkable characteristics in terms of variable gene usage, length of the third hypervariable loop of the classical antigen binding site (CDR-H3), and somatic mutation rate. These unusual properties may have profound impact on the specificity, affinity, and polyreactivity of the expressed IgE repertoire. 


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The Immunogenetics of Allergic Sensitization: Selection of the IgE Repertoire