title: Inhibition of human immunodeficiency virus type 1 gp120 presentation to CD4 T cells by antibodies specific for the CD4 binding domain of gp120.
abstract: Human immunodeficiency virus (HIV)-specific CD4 T-cell responses, particularly to the envelope glycoproteins of the virus, are weak or absent in most HIV-infected patients. Although these poor responses can be attributed simply to the destruction of the specific CD4 T cells by the virus, other factors also appear to contribute to the suppression of these virus-specific responses. We previously showed that human monoclonal antibodies (MAbs) specific for the CD4 binding domain of gp120 (gp120(CD4BD)), when complexed with gp120, inhibited the proliferative responses of gp120-specific CD4 T-cells. MAbs to other gp120 epitopes did not exhibit this activity. The present study investigated the inhibitory mechanisms of the anti-gp120(CD4BD) MAbs. The anti-gp120(CD4BD) MAbs complexed with gp120 suppressed gamma interferon production as well as proliferation of gp120-specific CD4 T cells. Notably, the T-cell responses to gp120 were inhibited only when the MAbs were added to antigen-presenting cells (APCs) during antigen pulse; the addition of the MAbs after pulsing caused no inhibition. However, the anti-gp120(CD4BD) MAbs by themselves, or as MAb/gp120 complexes, did not affect the presentation of gp120-derived peptides by the APCs to T cells. These MAb/gp120 complexes also did not inhibit the ability of APCs to process and present unrelated antigens. To test whether the suppressive effect of anti-gp120(CD4BD) antibodies is caused by the antibodies' ability to block gp120-CD4 interaction, APCs were treated during antigen pulse with anti-CD4 MAbs. These treated APCs remained capable of presenting gp120 to the T cells. These results suggest that anti-gp120(CD4BD) Abs inhibit gp120 presentation by altering the uptake and/or processing of gp120 by the APCs but their inhibitory activity is not due to blocking of gp120 attachment to CD4 on the surface of APCs.
authors.affiliation: New York VA Medical Center and New York University School of Medicine, New York, New York 10010, USA. hioec01@med.nyu.edu
authors.forename: C E
authors.initials: CE
authors.lastname: Hioe
authors.forename: M
authors.initials: M
authors.lastname: Tuen
authors.forename: P C
authors.initials: PC
authors.lastname: Chien
authors.forename: G
authors.initials: G
authors.lastname: Jones
authors.forename: S
authors.initials: S
authors.lastname: Ratto-Kim
authors.forename: P J
authors.initials: PJ
authors.lastname: Norris
authors.forename: W J
authors.initials: WJ
authors.lastname: Moretto
authors.forename: D F
authors.initials: DF
authors.lastname: Nixon
authors.forename: M K
authors.initials: MK
authors.lastname: Gorny
authors.forename: S
authors.initials: S
authors.lastname: Zolla-Pazner
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000378:metabolism; D001665:Binding Sites; D015704:CD4 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D007371:Interferon-gamma