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 role in HIV infection. The presence of these molecules on virions and target cells promotes virus infectivity and has previously been shown to hinder virus neutralization by anti-HIV antibodies. To delineate the effect of these molecules on neutralization of HIV-1, human monoclonal antibodies (MAbs) to V3 and the CD4-binding domain (CD4bd) of gp120 were examined in the presence of anti-LFA-1 MAbs. When either of two anti-LFA-1 MAbs was present, higher 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 when an anti-LFA-1 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-1 MAb was present during the initial 24 hr only, if added 24 hr after infection, or if present throughout the culture period. These data suggest that the anti-LFA-1 MAbs could act at different stages of HIV-1 infection, including the initial virus-cell interaction as well as during the amplification and spread of virus from cell to cell. These findings demonstrate the significant role of LFA-1 in HIV-1 infection and have important implications for evaluating the neutralizing activity of anti-HIV antibodies.
Hioe
C E
CE
Department of Pathology, New York University Medical Center and Manhattan VA Medical Center, New York 10010, USA.
Hildreth
J E
JE
Zolla-Pazner
S
S
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D004306:Dose-Response Relationship, Immunologic; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D009500:Neutralization Tests
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D016169:Lymphocyte Function-Associated Antigen-1