Anti-CD4-binding domain antibodies complexed with HIV type 1 glycoprotein 120 inhibit CD4+ T cell-proliferative responses to glycoprotein 120.
HIV-specific CD4+ helper T cell responses, particularly to the envelope glycoproteins, are usually weak or absent in the majority of HIV-seropositive individuals. Since antibodies, by their capacity to alter antigen uptake and processing, are known to have modulatory effects on CD4+ T cell responses, we investigated the effect of antibodies produced by HIV-infected individuals on the CD4+ T cell response to HIV-1 gp120. Proliferative responses of gp120-specific CD4+ T cells were inhibited in the presence of either serum immunoglobulin from HIV-infected individuals or human monoclonal antibodies specific for the CD4-binding domain (CD4bd) of gp120. Human monoclonal antibodies to other gp120 epitopes did not have the same effect. The anti-CD4bd antibodies complexed with gp120 suppressed T cell lines specific for varying gp120 epitopes but did not affect T cell proliferation to non-HIV antigens. Moreover, inhibition by the anti-CD4bd/gp120 complexes was observed regardless of the types of antigen-presenting cells used to stimulate the T cells. These results indicate that the presence of anti-CD4bd antibodies complexed with gp120 can strongly suppress CD4+ helper T responses to gp120.
Hioe
C E
CE
New York Veteran Affairs Medical Center and Department of Pathology, New York University School of Medicine, New York 10010, USA. hioec01@med.nyu.edu
Jones
G J
GJ
Rees
A D
AD
Ratto-Kim
S
S
Birx
D
D
Münz
C
C
Gorny
M K
MK
Tuen
M
M
Zolla-Pazner
S
S
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000821:virology; D000942:Antigens, Bacterial; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002460:Cell Line; D000939:Epitopes / Q000235:genetics; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D009169:Mycobacterium tuberculosis / Q000276:immunology
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000942:Antigens, Bacterial; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120