A Crystallin Fold in the Interleukin-4-inducing Principle of Schistosoma mansoni Eggs (IPSE/alpha-1) Mediates IgE Binding for Antigen-independent Basophil Activation

作者：Meyer N Helge; Mayerhofer Hubert; Tripsianes Konstantinos; Blindow Silke; Barths Daniela; Mewes Astrid; Weimar Thomas; Koehli Thies; Bade Steffen; Madl Tobias; Frey Andreas; Haas Helmut; Mueller Dieckmann Jochen^*; Sattler Michael; Schramm Gabriele

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290(36): 22111-22126.

DOI：10.1074/jbc.M115.675066

The IL-4-inducing principle from Schistosoma mansoni eggs (IPSE/alpha-1), the major secretory product of eggs from the parasitic worm S. mansoni, efficiently triggers basophils to release the immunomodulatory key cytokine interleukin-4. Activation by IPSE/alpha-1 requires the presence of IgE on the basophils, but the detailed molecular mechanism underlying activation is unknown. NMR and crystallographic analysis of IPSE Delta NLS, a monomeric IPSE/alpha-1 mutant, revealed that IPSE/alpha-1 is a new member of the beta gamma-crystallin superfamily. We demonstrate that this molecule is a general immunoglobulin-binding factor with highest affinity for IgE. NMR binding studies of IPSE Delta NLS with the 180-kDa molecule IgE identified a large positively charged binding surface that includes a flexible loop, which is unique to the IPSE/alpha-1 crystallin fold. Mutational analysis of amino acids in the binding interface showed that residues contributing to IgE binding are important for IgE-dependent activation of basophils. As IPSE/alpha-1 is unable to cross-link IgE, we propose that this molecule, by taking advantage of its unique IgE-binding crystallin fold, activates basophils by a novel, cross-linking-independent mechanism.

• 出版日期2015-9-4