Document 0403
 DOCN  M9550403
 TI    Recombinant CD4-IgE, a novel hybrid molecule, inducing basophils to
       respond to human immunodeficiency virus (HIV) and HIV-infected target
       cells.
 DT    9505
 AU    Krauss S; Kufer P; Federle C; Tabaszewski P; Weiss E; Rieber EP;
       Riethmuller G; Institute for Immunology, University of Munich, Germany.
 SO    Eur J Immunol. 1995 Jan;25(1):192-9. Unique Identifier : AIDSLINE
       MED/95145526
 AB    Basophils and mast cells, as the main effector cells in IgE-mediated
       type I hypersensitivity, are involved in the elimination of parasites
       and, according to recent findings, may also play an important role in
       the defense against bacterial and viral infections. Using a genetic
       engineering approach we wanted to redirect this potent IgE-mediated
       defense system against intruding human immune deficiency virus. We
       constructed a recombinant CD4-IgE molecule, consisting of the two
       N-terminal domains of CD4 and the CH2-4 domains of the IgE heavy chain,
       thus providing the IgE with specificity for the gp120 of human
       immunodeficiency virus (HIV). The binding properties of hybrid CD4-IgE
       to the high-affinity receptor for IgE (Fc epsilon RI) on basophils as
       well as to the low-affinity receptor (Fc epsilon RII or CD23) for IgE on
       lymphoid cells were found to be similar to those of native IgE. At the
       same time, the CD4 domains of the recombinant molecule retained the
       gp120 binding specificity with an affinity similar to that of the native
       CD4. By functional tests, we demonstrated that CD4-IgE armed basophils
       can be triggered by free HIV and by HIV-infected cells to release their
       mediators. We further show that HIV-triggered basophils lead to a
       decreased replication of HIV in susceptible T cells. We, therefore,
       conclude that the type I hypersensitivity effector cells can be engaged
       in the elimination of HIV-infected cells, at least in vitro. Because of
       the strong binding of the CD4-IgE construct to the Fc epsilon RI, we
       assume that CD4-IgE has a short t1/2 in serum, but may similarly to IgE
       exhibit prolonged resident time on basophils and mast cells, which are
       located close to mucosal surfaces or in the connective tissue. Thus
       CD4-IgE could play an important role in the elimination of HIV also in
       vivo.
 DE    Antigens, CD4/BIOSYNTHESIS/*IMMUNOLOGY  Basophils/*IMMUNOLOGY  Blotting,
       Western  Cells, Cultured  Cytotoxicity Tests, Immunologic  Histamine
       Liberation/IMMUNOLOGY  Human  HIV/*IMMUNOLOGY  HIV Antigens/IMMUNOLOGY
       IgE/BIOSYNTHESIS/*IMMUNOLOGY  Receptors, IgE/METABOLISM  Recombinant
       Fusion Proteins/BIOSYNTHESIS/IMMUNOLOGY  Support, Non-U.S. Gov't
       JOURNAL ARTICLE

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