Ce. Hioe et al., Inhibition of human immunodeficiency virus type 1 gp120 presentation to CD4 T cells by antibodies specific for the CD4 binding domain of gp120, J VIROLOGY, 75(22), 2001, pp. 10950-10957
Human immunodeficiency virus (HIV)-specific CD4 T-cell responses, particula
rly to the envelope glycoproteins of the virus, are weak or absent in most
HIV-infected patients. Although these poor responses can be attributed simp
ly to the destruction of the specific CD4 T cells by the virus, other facto
rs also appear to contribute to the suppression of these virus-specific res
ponses. We previously showed that human monoclonal antibodies (MAbs) specif
ic 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 st
udy investigated the inhibitory mechanisms of the anti-gp120(CD4BD) MAbs. T
he 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 t
he MAbs after pulsing caused no inhibition. However, the anti-gp120(CD4BD)
MAbs by themselves, or as MAb/gp120 complexes, did not affect the presentat
ion of gp120-derived peptides by the APCs to T cells. These MAb/gp120 compl
exes also did not inhibit the ability of APCs to process and present unrela
ted antigens. To test whether the suppressive effect of anti-gp120(CD4BD) a
ntibodies is caused by the antibodies' ability to block gp120-CD4 interacti
on, APCs were treated during antigen pulse with anti-CD4 MAbs. These treate
d APCs remained capable of presenting gp120 to the T cells. These results s
uggest that anti-gp120(CD4BD) Abs inhibit gp120 presentation by altering th
e uptake and/or processing of gp120 by the APCs but their inhibitory activi
ty is not due to blocking of gp120 attachment to CD4 on the surface of APCs
.