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4,4'-二异硫氰酸根合芪-2,2'-二磺酸与人细胞CD4的特异性相互作用

Specific interaction of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid with human cellular CD4.

作者信息

Schroeder K, Bowlin T L, Bridges G, Taylor D, Tyms A S, Cardin A D

机构信息

Marion Merrell Dow Research Institute, Cincinnati, Ohio 45215.

出版信息

Cell Immunol. 1994 Nov;159(1):103-10. doi: 10.1006/cimm.1994.1299.

DOI:10.1006/cimm.1994.1299
PMID:7954838
Abstract

We recently demonstrated that 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) prevented the infection of T cells by human immunodeficiency virus type-1 (Cardin et al., J. Biol. Chem. 266, 13355, 1991). In the present study we have used a panel of monoclonal antibodies (mabs) against a variety of human leukocyte antigens to characterize the interaction of DIDS by flow cytometry with various T cell surface molecules. DIDS blocked the specific immunoreactivity of mabs OKT4A and Leu 3A with CD4 on human leukemic T cells (JM) and human mononuclear lymphocytes with an IC50 approximately 30 microM. The membrane distal (D1) and proximal (D3 and D4) domains of CD4 remained blocked for up to 5 hr of culture and returned to control levels of expression after 24 hr, reflecting the rate of membrane turnover of the CD4-DIDS complex. The binding frequencies (% positive) for anti-CD2, -CD3, -CD5, -CD6, -CD7, -CD8, -CD11a, -CD14, -CD18, -CD19, -CD45, -T cell receptor, and -HLA-DR were not significantly affected. However, there was a partial reduction in the antigen density of CD2, CD5, CD8, and CD11b. The selective interaction of DIDS with CD4 suggests that antagonism of the virus receptor may account in part for the antiviral properties of the stilbene disulfonate.

摘要

我们最近证明,4,4'-二异硫氰酸根合芪-2,2'-二磺酸(DIDS)可预防人类免疫缺陷病毒1型对T细胞的感染(Cardin等人,《生物化学杂志》,第266卷,第13355页,1991年)。在本研究中,我们使用了一组针对多种人类白细胞抗原的单克隆抗体,通过流式细胞术来表征DIDS与各种T细胞表面分子的相互作用。DIDS可阻断单克隆抗体OKT4A和Leu 3A与人类白血病T细胞(JM)和人类单核淋巴细胞上CD4的特异性免疫反应,其半数抑制浓度(IC50)约为30微摩尔。CD4的膜远端(D1)和近端(D3和D4)结构域在培养长达5小时后仍被阻断,24小时后恢复到对照表达水平,这反映了CD4-DIDS复合物的膜周转速率。抗CD2、-CD3、-CD5、-CD6、-CD7、-CD8、-CD11a、-CD14、-CD18、-CD19、-CD45、-T细胞受体和-HLA-DR的结合频率(阳性百分比)未受到显著影响。然而,CD2、CD5、CD8和CD11b的抗原密度有部分降低。DIDS与CD4的选择性相互作用表明,病毒受体的拮抗作用可能部分解释了二苯乙烯二磺酸盐的抗病毒特性。

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