title: Potency of HIV-1 envelope glycoprotein gp120 antibodies to inhibit the interaction of DC-SIGN with HIV-1 gp120.
abstract: The interaction of DC-SIGN with gp120 provides an attractive target for intervention of HIV-1 transmission. Here, we have investigated the potency of gp120 antibodies to inhibit the DC-SIGN-gp120 interaction. We demonstrate that although the V3 loop is not essential for DC-SIGN binding, antibodies against the V3 loop partially inhibit DC-SIGN binding, suggesting that these antibodies sterically hinder DC-SIGN binding to gp120. Polyclonal antibodies raised against non-glycosylated gp120 inhibited both low and high avidity DC-SIGN-gp120 interactions in contrast to polyclonal antibodies raised against glycosylated gp120. Thus, glycans present on gp120 may prevent the generation of antibodies that block the DC-SIGN-gp120 interactions. Moreover, the polyclonal antibodies against non-glycosylated gp120 efficiently inhibited HIV-1 capture by both DC-SIGN transfectants and immature dendritic cells. Therefore, non-glycosylated gp120 may be an attractive immunogen to elicit gp120 antibodies that block the binding to DC-SIGN. Furthermore, we demonstrate that DC-SIGN binding to gp120 enhanced CD4 binding, suggesting that DC-SIGN induces conformational changes in gp120, which may provide new targets for neutralizing antibodies.
authors.affiliation: Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Annemarie N
authors.initials: AN
authors.lastname: Lekkerkerker
authors.forename: Irene S
authors.initials: IS
authors.lastname: Ludwig
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: van Vliet
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions; D015704:CD4 Antigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002478:Cells, Cultured; D006031:Glycosylation; D015483:HIV Antibodies / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology*; D051379:Mice; D011956:Receptors, Cell Surface / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin