Tobias Rogosch - Composition of the immunoglobulin classic antigen-binding site regulates allergic airway inflammation in a murine model of experimental asthma.

Version 2

      Publication Details (including relevant citation   information):

      Kerzel S, Wagner J, Rogosch T, Yildirim AO, Sikula L, Fehrenbach   H, Garn H, Maier RF, Schroeder HW Jr, Zemlin M.

      Clin Exp Allergy. 2009 Apr;39(4):591-601

      doi: 10.1111/j.1365-2222.2008.03178.x

      Abstract:

      BACKGROUND: When bound to mast cell FcepsilonRI, IgE serves as   antigen receptor for allergic reactions, permitting specific   identification of the allergen. Although the core of the classic   antigen-binding site is heavy chain complementarity determining   region 3 (CDR-H3), recent studies suggest that allergens might   also bind IgE in a superantigen-like fashion outside the classic   antigen-binding site.

      OBJECTIVE: We sought to evaluate the contribution of the classic   CDR-H3-centric antigen-binding site to the development of an   allergic phenotype.

      METHODS: Using a murine model of experimental asthma, we   characterized a gene-targeted mouse strain expressing an altered   range of CDR-H3s (DeltaD-iD mice) in response to the hydrophobic   allergen ovalbumin (OVA). Mutant and wild-type (wt) mice were   sensitized intraperitoneally with OVA; non-sensitized mice served   as controls.

      RESULTS: We found the composition of the classic CDR-H3-centric   antigen-binding site to be critical for the development of   characteristic aspects of allergic asthma. (i) Compared with wt   animals, DeltaD-iD mice showed a significantly less pronounced   OVA-induced rise in allergen-specific IgE levels and hence in   total serum IgE levels. (ii) In addition, DeltaD-iD mice   demonstrated a significant reduction in eosinophilic airway   inflammation, as well as in interleukin-4 (IL-4), IL-5 and IL-13   levels in BAL fluids.

      CONCLUSION: Allergic sensitization and airway inflammation depend   on the composition of the predominant CDR-H3 repertoire,   suggesting that the classic CDR-H3-centric antigen-binding site   plays a crucial role in creating the immunological interface   between allergen and IgE. Our results further emphasize a central   role of IgE, not only in mediating but also in regulating the   allergic immune response.

      Address (URL): http://www.ncbi.nlm.nih.gov/pubmed/19220320