An HIV-1-seropositive volunteer was infused with an expanded autologous cytotoxic T lymphocyte (CTL) clone directed against the HIV-1 nef protein. This clone was adoptively transferred to determine whether supplementing CTL activity could reduce viral load or improve clinical course. Unexpectedly, infusion was followed by a decline in circulating CD4+ T cells and a rise in viral load. Some of the HIV isolates obtained from the plasma or CD4+ cells of the patient were lacking the nef epitope. These results suggest that active CTL selection of viral variants could contribute to the pathogenesis of AIDS and that clinical progression can occur despite high levels of circulating HIV-1-specific CTLs.
A human immunoglobulin Gi lambda monoclonal antibody (MAb), 697-D, was developed that recognizes the V2 region of human immunodeficiency virus type 1 (HIV-1) gpl20. Substitutions at amino acid positions 176/177, 179/180, 183/184, and 192 to 194 in the V2 loop of gpl20 each completely abolished the binding capacity of 697-D in an enzyme-linked immunosorbent assay format. Competition analysis with three different neutralizing murine anti-V2 MAbs confirmed the specificity of 697-D. The 697-D epitope is primarily conformation dependent, although there was weak reactivity of the MAb with a V2 peptide spanning residues 161 to 180. Treatment of recombinant gpl20 HIVIIIB with sodium metaperiodate, which oxidizes carbohydrates, abolished the binding of the MAb, showing the dependence of the epitope on intact carbohydrates. The broad reactivity of 697-D was displayed by its binding to the gpl20 molecules from four of four laboratory isolates and five of five primary isolates. The MAb 697-D neutralized three out of four primary isolates but failed to neutralize any of four laboratory strains of HIV-1. 697-D and a human anti-V3 MAb, 447-52-D, displayed similar potency in neutralizing primary isolates, indicating that the V2 region of gpl20, like the V3 region and the CD4-binding domain, can induce potent neutralizing antibodies against HIV-1 in humans.
Human monoclonal antibody 447-52D binds to the V3 determinant of the human immunodeficiency virus type 1 (HIV-1) gpl20 external glycoprotein. Its binding requires the expression of the GPxR sequence at the center of the V3 domain. HIV-1 variants that are adapted to replication in T-lymphoid cell lines and express this sequence motif are efficiently neutralized by the antibody (
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