کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2830937 1570730 2012 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
CɛmX peptide-carrying HBcAg virus-like particles induced antibodies that down-regulate mIgE-B lymphocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
CɛmX peptide-carrying HBcAg virus-like particles induced antibodies that down-regulate mIgE-B lymphocytes
چکیده انگلیسی

Type-I hypersensitivity reactions play a critical role in the pathogenesis of various allergic diseases. The successful development of the anti-IgE antibody, omalizumab, has validated IgE as an effective therapeutic target for the treatment of various IgE-mediated allergic diseases. Two research groups have reported that mAbs specific for certain parts of CɛmX, a domain of 52 aa residues in human membrane-bound IgE (mIgE), can cause the lysis of mIgE-B cells by apoptosis and antibody-dependent cellular cytotoxicity (ADCC). Herein, we explore virus-like particles formed by hepatitis B virus core antigen (HBcAg) that harbors the entire CɛmX peptide or its fragments as immunogens for inducing anti-CɛmX antibodies. The results showed that mice immunized subcutaneously with these immunogens produced antibodies that bind to recombinant CɛmX-containing human IgE.Fc in ELISA and Western blot analyses, and to genetically engineered human mIgE-expressing Ramos B cell line in fluorescence flow cytometric assays. The IgG antibodies purified from the sera of immunized mice were able to cause the apoptosis of mIgE-expressing Ramos cells through a BCR-dependent caspase pathway. Furthermore, the IgG could mediate ADCC in human mIgE-expressing A20 murine B-cell lymphoma. These studies suggest that HBcAg-CɛmX peptide immunogens warrant further investigation as a therapeutic modality for modulating IgE in patients with IgE-mediated allergic diseases.


► Membrane-bound IgE (mIgE) is a molecular target for immunological targeting of mIgE-expressing B lymphocytes.
► The CɛmX (also referred to as M1′) segment, located between the CH4 domain and the membrane-anchor peptide of the ɛ chain of mIgE, is a unique antigenic site.
► Immunogens based on CɛmX and hepatitis B core antigen as a carrier protein can elicit antibodies that down-regulate mIgE+ B cells.
► Such immunogens may potentially be vaccine-like therapeutics for IgE-mediated allergic diseases.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 52, Issues 3–4, October–December 2012, Pages 190–199
نویسندگان
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