title: Nonneutralizing antibodies to the CD4-binding site on the gp120 subunit of human immunodeficiency virus type 1 do not interfere with the activity of a neutralizing antibody against the same site.
abstract: We have investigated whether nonneutralizing monoclonal antibodies (MAbs) to the gp120 subunit of the envelope glycoprotein (Env) complex of human immunodeficiency virus type 1 (HIV-1) can interfere with HIV-1 neutralization by another anti-gp120 MAb. We used neutralizing (b12) and nonneutralizing (205-42-15, 204-43-1, 205-46-9) MAbs to the epitope cluster overlapping the CD4-binding site (CD4BS) on gp120. All the MAbs, neutralizing or otherwise, cross-competed for binding to monomeric gp120, indicating the close topological proximity of their epitopes. However, the nonneutralizing CD4BS MAbs did not interfere with the neutralization activity of MAb b12. In contrast, in a binding assay using oligomeric Env expressed on the surface of Env-transfected cells, the nonneutralizing MAbs did partially compete with b12 for Env binding. The surface of Env-transfected cells contains two categories of binding site for CD4BS MAbs. One type of site is recognized by both b12 and nonneutralizing CD4BS MAbs; the other is recognized by only b12. Binding assays for Env-gp120 interactions based on the use of monomeric gp120 or Env-transfected cells do not predict the outcome of HIV-1 neutralization assays, and they should therefore be used only with caution when gauging the properties of anti-Env MAbs.
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Herrera
authors.forename: Catherine
authors.initials: C
authors.lastname: Spenlehauer
authors.forename: Michael S
authors.initials: MS
authors.lastname: Fung
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Simon
authors.initials: S
authors.lastname: Beddows
authors.forename: John P
authors.initials: JP
authors.lastname: Moore
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D009500:Neutralization Tests
chemical_list: D016915:AIDS Vaccines; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120