Tobias Rogosch - The Immunogenetics of Allergic Sensitization: Selection of the IgE Repertoire

Version 2

      Publication Details (including relevant citation   information):

      Zemlin M, Rogosch T, Kerzel S.

      in: MA Osborne, Advances in Genetics Research, Volume 1.   Hauppauge NY 2010 (Nova Science Publishers)


      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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