EFFECT OF ANTIBODY VALENCY ON INTERACTION WITH CELL-SURFACE EXPRESSEDHIV-1 AND VIRAL NEUTRALIZATION

F(ab) and F(ab')(2) fragments of the human mAb, F105, were compared to intact IgG1 for binding to the CD4 binding site of HIV-1/gp120 on the surface of infected cells and viral neutralization. F105 IgG1 and F(a b')(2) bound to IIIB, MN, and RF infected cells and neutralized these strains in an identical fashion, whereas strain-specific differences w ere observed in F(ab) activity. Although F105 F(ab) bound with equival ent affinity to IIIB-infected cells, there was a 4- to 10-fold decreas e in the neutralization of IIIB by monovalent F(ab) compared to the bi valent molecules. F105 F(ab) demonstrated both diminished binding and neutralization of the MN strain and failed to bind or neutralize the R F strain. When cooperativity of V3 loop antibody (V3ab) with F105 IgG and fragments was examined, the binding of F105 IgG and F(ab')(2) to I IIB-, MN-, or RF-infected cells was modestly enhanced by V3ab; viral n eutralization was substantially enhanced by the combination of V3ab an d F105 IgG and F(ab')(2). The combination of F105 F(ab) with V3ab also resulted in significant cooperative neutralization of IIIB and MN, bu t the lack of F105 F(ab) binding and neutralization of RF was unaltere d by V3ab. These results suggest that bivalent interaction may be impo rtant in binding and neutralization of virus, and support the notion t hat this interaction may depend on conformational changes in oligomeri c gp120 on intact virions and cell surface rather than on affinity or steric effects.