INHIBITION OF HIV-1 RGP120 BINDING TO CD4(-CELLS BY MONOCLONAL-ANTIBODIES DIRECTED AGAINST THE GP120 C1 OR C4 LEGION() T)

Reagents which block the interaction of HIV-1 gp120 with CD4(+) T cell are of therapeutic interest. We assessed the ability of the murine mo noclonal antibody (mAb) 87-135/9 to bind to the rgp120 Cl region and t o block the CD4 inter-action, and compared this with the reactivity of the rat mAb 388/389 or the human mAbs F105 and b12, which are known t o bind within or near the gp120 C4 region. ELISA and surface plasmon r esonance measurements showed that mAb 87-135/9 recognized specifically the gp120 CI peptide HEDIISLWDQSLK (residues 105-117). All four mAbs bound to rgp120 and blocked its interaction with CD4(+) T cells. When mAb 87-135/9 was used in combination with one of the other antibodies, its inhibitory effect was additive. A therapeutic approach could be t o use a human anti-gp120/CD4bs conformational mAb in combination with a humanized Ab directed against the conserved, linear gp120 Cl epitope and/or an anti-viral drug to hinder the HIV-1 virus and shedded envel ope protein to bind to CD4(+) T cells. (C) 1998 Elsevier Science B.V. All rights reserved.