• Jiun-Bo Chen, Louisa K James, Anna M Davies, Yu-Chang Bryan Wu, Joanne Rimmer, Valerie J Lund, Jou-Han Chen, James M McDonnell, Yih-Chih Chan, George H Hutchins, Tse Wen Chang, Brian J Sutton, Harsha H Kariyawasam, and Hannah J Gould.
• Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
• J. Allergy Clin. Immunol. 2017 Apr 1; 139 (4): 1195-1204.e11.

BackgroundChronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti-SAEs.ObjectivesWe aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions.MethodsLabeled staphylococcal enterotoxin (SE) A, SED, and SEE were used to isolate single SAE-specific B cells from the nasal polyps of 3 patients with aspirin-exacerbated respiratory disease by using fluorescence-activated cell sorting. Recombinant antibodies with "matched" heavy and light chains were cloned as IgG1, and those of high affinity for specific SAEs, assayed by means of ELISA and surface plasmon resonance, were recloned as IgE and antigen-binding fragments. IgE activities were tested in basophil degranulation assays.ResultsThirty-seven SAE-specific, IgG- or IgA-expressing B cells were isolated and yielded 6 anti-SAE clones, 2 each for SEA, SED, and SEE. Competition binding assays revealed that the anti-SEE antibodies recognize nonoverlapping epitopes in SEE. Unexpectedly, each anti-SEE mediated SEE-induced basophil degranulation, and IgG1 or antigen-binding fragments of each anti-SEE enhanced degranulation by the other anti-SEE.ConclusionsSEEs can activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti-SEE IgE in anti-SEE IgE-FcεRI complexes. Anti-SEE IgG1s can enhance the activity of anti-SEE IgEs as conventional antibodies through CDRs or simultaneously as conventional antibodies and as "superantibodies" through CDRs and framework regions to SEEs in SEE-anti-SEE IgE-FcεRI complexes.Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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