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РЖ ВИНИТИ 34 (BI39) 95.12-04К1.692

Recombinant CD4-IgE, a novel hybrid molecule, inducing basophils to respond to human immunodeficiency vitus (HIV) and HIV-infected target cells [Text] / Susanne Krauss [et al.] // Eur. J. Immunol. - 1995. - Vol. 25, N 1. - P192-199 . - ISSN 0014-2980
Перевод заглавия: Рекомбинант CD4-IgE, новая гибридная молекула, вызывающая ответ базофилов на вирус иммунодефицита человека (ВИЧ) и зараженные ВИЧ клетки-мишени
Аннотация: 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 CH[2-4] 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['эпсилон']RI) on basophils as well as to the low-affinity receptor (Fc['эпсилон']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['эпсилон']RI, we assume that CD4-IgE has a short t[1/2] 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. Германия, Inst. Immunol., Univ. Munchen. Библ. 39

ГРНТИ	34.43.41

ВИНИТИ 341.43.41.13.05
Рубрики: МОЛЕКУЛА IGE-CD4
ПРОТИВОВИРУСНАЯ АКТИВНОСТЬ
ВИРУС ИММУНОДЕФИЦИТА ЧЕЛОВЕКА
ЗАРАЖЕННЫЕ КЛЕТКИ
ЧЕЛОВЕК

Доп.точки доступа:
Krauss, Susanne; Kufer, Peter; Federle, Christine; Tabaszewski, Pjotr; Weiss, Elisabeth; Rieber, E.Peter; Riethmuller, Gert

РЖ ВИНИТИ 34 (BI11) 96.01-04Б1.309

Recombinant CD4-IgE, a novel hybrid molecule, inducing basophils to respond to human immunodeficiency vitus (HIV) and HIV-infected target cells [Text] / Susanne Krauss [et al.] // Eur. J. Immunol. - 1995. - Vol. 25, N 1. - P192-199 . - ISSN 0014-2980
Перевод заглавия: Рекомбинант CD4-IgE, новая гибридная молекула, вызывающая ответ базофилов на вирус иммунодефицита человека (ВИЧ) и зараженные ВИЧ клетки-мишени
Аннотация: 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 CH[2-4] 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['эпсилон']RI) on basophils as well as to the low-affinity receptor (Fc['эпсилон']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['эпсилон']RI, we assume that CD4-IgE has a short t[1/2] 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. Германия, Inst. Immunol., Univ. Munchen. Библ. 39

ГРНТИ	34.25.23

ВИНИТИ 341.25.23.17
Рубрики: МОЛЕКУЛА IGE-CD4
ПРОТИВОВИРУСНАЯ АКТИВНОСТЬ
ВИРУС ИММУНОДЕФИЦИТА ЧЕЛОВЕКА
ЗАРАЖЕННЫЕ КЛЕТКИ
ЧЕЛОВЕК

Доп.точки доступа:
Krauss, Susanne; Kufer, Peter; Federle, Christine; Tabaszewski, Pjotr; Weiss, Elisabeth; Rieber, E.Peter; Riethmuller, Gert

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