Specific interaction of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid with human cellular CD4.
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.
Marion Merrell Dow Research Institute, Cincinnati, Ohio 45215.
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D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000737:chemistry*; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000187:drug effects; D015704:CD4 Antigens / Q000737:chemistry* / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D006684:HLA-DR Antigens; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid