Enhanced HIV type 1 neutralization by human anti-glycoprotein 120 monoclonal antibodies in the presence of monoclonal antibodies to lymphocyte function-associated molecule 1

Cellular adhesion receptor LFA-1 and its ICAM ligands are known to play a r ole in HIV infection. The presence of these molecules on virions and target cells promotes virus infectivity and has previously been shown to hinder v irus neutralization by anti-HIV antibodies. To delineate the effect of thes e molecules on neutralization of HIV-1, human monoclonal antibodies (MAbs) to V3 and the CD4-binding domain (CD4bd) of gp120 were examined in the pres ence of anti-LFA-1 MAbs. When either of two anti-LFA-l MAbs was present, hi gher levels of virus neutralization were achieved by both anti-V3 and anti- CD4bd MAbs, This effect was observed with primary HIV-1 isolates as well as with a laboratory-adapted strain, However, this activity was seen only whe n an anti-LFA-l MAb was combined with anti-gp120 MAbs that exhibited virus- specific neutralizing activities, demonstrating the specificity of both the anti-LFA-1 and anti-gp120 MAbs, Enhanced neutralization by anti-gp120 MAbs was observed if the anti-LFA.-l MAb was present during the initial 24 hr o nly, if added 24 hr after infection, or if present throughout the culture p eriod. These data suggest that the anti-LFA-l MAbs could act at different s tages of HIV-1 infection, including the initial virus-cell interaction as w ell as during the amplification and spread of virus from cell to cell. Thes e findings demonstrate the significant role of LFA-1 in HIV-1 infection and have important implications for evaluating the neutralizing activity of an ti-HIV antibodies.