title: Characterization of CD4-induced epitopes on the HIV type 1 gp120 envelope glycoprotein recognized by neutralizing human monoclonal antibodies.
abstract: The entry of human immunodeficiency virus (HIV-1) into target cells typically requires the sequential binding of the viral exterior envelope glycoprotein, gp120, to CD4 and a chemokine receptor. CD4 binding exposes gp120 epitopes recognized by CD4-induced (CD4i) antibodies, which can block virus binding to the chemokine receptor. We identified three new CD4i antibodies from an HIV-1-infected individual and localized their epitopes. These epitopes include a highly conserved gp120 beta-strand encompassing residues 419-424, which is also important for binding to the CCR5 chemokine receptor. All of the CD4i antibodies inhibited the binding of gp120-CD4 complexes to CCR5. CD4i antibodies and CD4 reciprocally induced each other's binding, suggesting that these ligands recognize a similar gp120 conformation. The CD4i antibodies neutralized laboratory-adapted HIV-1 isolates; primary isolates were more resistant to neutralization by these antibodies. Thus, all known CD4i antibodies recognize a common, conserved gp120 element overlapping the binding site for the CCR5 chemokine receptor.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, USA.
authors.forename: Shi-Hua
authors.initials: SH
authors.lastname: Xiang
authors.forename: Najah
authors.initials: N
authors.lastname: Doka
authors.forename: Rabeéa K
authors.initials: RK
authors.lastname: Choudhary
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
authors.forename: James E
authors.initials: JE
authors.lastname: Robinson
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D011487:Protein Conformation
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120