title: Human immunodeficiency virus type 1 neutralization is determined by epitope exposure on the gp120 oligomer.
abstract: The major target of the neutralizing antibody response to infection by the human immunodeficiency virus type 1 (HIV-1) is the outer envelope glycoprotein, gp120. The spectrum of HIV-1 neutralization specificity is currently represented by monoclonal antibodies (mAbs) that can be divided broadly into five groups. We have studied the binding of these mAbs to functional oligomeric and soluble monomeric gp120 derived from the molecular clone of a cell line-adapted isolate of HIV-1, and compared these binding properties with virus neutralization. Binding of all mAbs except those reactive with the V3 loop was much weaker to oligomeric than to monomeric gp120. This reduction in binding to oligomeric gp120 was determined mostly by a slower relative rate of association, although the dissociation rate also had some influence on relative variation in mAb affinity. Virus neutralization correlated broadly with mAb binding to the oligomeric rather than to the monomeric form of gp120, and neutralization potency was related to the estimated association rate. Thus, with the exception of the hypervariable V3 loop, regions of HIV-1 gp120 with the potential to induce a neutralization response are likely to be poorly presented for antibody recognition on the surface of cell line-adapted virions.
authors.affiliation: Centre d'Immunologie de Marseille Luminy, Marseille, France.
authors.forename: Q J
authors.initials: QJ
authors.lastname: Sattentau
authors.forename: J P
authors.initials: JP
authors.lastname: Moore
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D000915:Antibody Affinity; D000937:Antigen-Antibody Reactions; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism; D015483:HIV Antibodies / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D014771:Virion / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments