Increased association of glycoprotein 120-CD4 with HIV type 1 coreceptors in the presence of complex-enhanced anti-CD4 monoclonal antibodies.
CD4-specific monoclonal antibodies (CG1, CG7, and CG8), which bind with a 5- to 10-fold higher avidity to preformed CD4-gp120 complexes than to CD4, were previously shown to recognize newly identified conformational epitopes in the D1-CDR3 region of CD4. In the current study, these and other complex-enhanced MAbs were tested in three separate assays of HIV-1 coreceptor (CXCR4/CCR5) recruitment. In these assays, the CD4-specific MAbs CG1, -7, and -8 stabilized the association of coreceptor, gp120, and CD4 in trimolecular complexes. In contrast, the gp120-specific, complex-enhanced MAbs 48d and 17b were inhibitory. These data suggest that conformational changes in the CDR3 region of CD4-D1, induced by gp120 binding, may be involved in coreceptor association and thus play a positive role in the HIV-1 cell fusion process.
Division of viral products, CBER, Food and Drug Administration, Bethesda, Maryland 20892, USA. goldingh@cber.fda.gov
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Golding
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Ouyang
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Zaitseva
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D000911:Antibodies, Monoclonal / Q000378:metabolism*; D015704:CD4 Antigens / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000378:metabolism; D019169:Jurkat Cells; D011233:Precipitin Tests; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D007135:Immunoglobulin Variable Region; D019713:Receptors, CCR5; D019718:Receptors, CXCR4