A molecular mechanism of inhibition of HIV-1 binding to CD4+ cells by monoclonal antibodies to gp110.
We have investigated the possible involvement in the interaction between HIV gp110 and its CD4 receptor of epitopes different from the currently known binding site(s) of the molecule. Four monoclonal antibodies (MAbs) to gp110 were used (Genetic Systems Corporation, Seattle, Washington, USA): one (110-1) recognized a peptide corresponding to the C-terminal part of gp110 (494-517); the other three (110-3, 110-4, 110-5) recognized the same peptide located at position 308-328. HIV or purified gp110 obtained from a vaccinia recombinant (Transgene S.A., Strasbourg, France) were pre-incubated with the MAb prior to addition to CD4+ cells. Specific binding of viral particles or of the soluble molecule was then determined by flow cytometer analysis, compared with that of control preparations where the MAb was added after HIV or gp 110 had been allowed to bind CD4+ cells. Significant inhibition of HIV binding was noted with the three MAbs to peptide (308-328), but not with 110-1. At the molecular level, these same MAbs decreased the affinity of interaction between CD4 and soluble gp110, although they could still label the latter molecule after it had bound to CD4+ cells. Therefore, steric hindrance may account for neutralization of HIV binding by antibodies that are actually directed to epitopes topographically distinct from the site of binding of gp110 to CD4.
Bahraoui
E
E
Unité d'Oncologie Virale, Institut Pasteur, Paris, France.
Clerget-Raslain
B
B
Chapuis
F
F
Olivier
R
R
Parravicini
C
C
Yagello
M
M
Montagnier
L
L
Gluckman
J C
JC
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000939:Epitopes; D006678:HIV / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D015728:Receptors, HIV; D011991:Receptors, Virus / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D008562:Membrane Glycoproteins; D015728:Receptors, HIV; D011991:Receptors, Virus; C030340:elastin microfibril interface located protein