title: IgE-tailpiece associates with α-1-antitrypsin (A1AT) to protect IgE from proteolysis without compromising its ability to interact with FcεRI.
abstract: Several splice variants of IgE exist in human plasma, including a variant called IgE-tailpiece (IgE-tp) that differs from classical IgE by the replacement of two carboxy-terminal amino acids with eight novel residues that include an ultimate cysteine. To date, the role of the secreted IgE-tp isoform in human immunity is unknown. We show that levels of IgE-tp are raised in helminth-infected donors, and that both the classical form of IgE (IgE-c) and IgE-tp interact with polymers of the serine protease inhibitor alpha-1-antitrypsin (A1AT). The association of IgE-tp with A1AT polymers in plasma protects the antibody from serine protease-mediated degradation, without affecting the functional interaction of IgE-tp with important receptors, including FcεR1. That polymers of A1AT protect IgE from degradation by helminth proteases may explain why these common and normally non-disease causing polymorphic variants of A1AT have been retained by natural selection. The observation that IgE can be complexed with polymeric forms of A1AT may therefore have important consequences for our understanding of the pathophysiology of pulmonary diseases that arise either as a consequence of A1AT-deficiency or through IgE-mediated type 1 hypersensitivity responses.
authors: Institute of Genetics, School of Biology, University of Nottingham, Nottingham NG7 2UH, UK.
authors: Phyllis M
authors: PM
authors: Quinn
authors: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors: David W
authors: DW
authors: Dunne
authors: Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.|Warwick Systems Biology Centre, Senate House, University of Warwick, Coventry CV47 7AL, UK.
authors: Shona C
authors: SC
authors: Moore
authors: Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
authors: Richard J
authors: RJ
authors: Pleass
mesh_terms: D006373:Helminthiasis / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D059748:Proteolysis; D017455:Receptors, IgE / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D017455:Receptors, IgE; D000515:alpha 1-Antitrypsin; D007073:Immunoglobulin E