ANTIBODIES TO THE HIV-1 V3 LOOP IN SERUM FROM INFECTED PERSONS CONTRIBUTE A MAJOR PROPORTION OF IMMUNE EFFECTOR FUNCTIONS INCLUDING COMPLEMENT ACTIVATION, ANTIBODY-BINDING, AND NEUTRALIZATION

Previous studies have shown that the V3 region of the HIV envelope is both critical to viral functions and immunogenic. However, the relativ e contribution of anti-V3 antibodies in the sera of infected individua ls in mediating immune effector functions directed at whole intact vir us and infected cells has not been determined. This study used peptide s corresponding to several regions of the HIV envelope as inhibitors o f antibody binding and antibody effector functions directed at virions and virus-infected cells in order to assess the relative importance o f V3-specific antibodies in sera from infected persons. Approximately 40% of the antibody in serum which could bind to native viral proteins on HIVMN-infected cells was blocked by a peptide corresponding to the central 15 amino acids of the V3 loop. In contrast, little if any blo cking of serum antibody binding was observed with peptides correspondi ng to flanking regions of HIVMN V3 or three regions of gp41. Since ant iviral antibody can also activate immune effector functions, we determ ined whether peptides could block antibody-dependent activation of the complement system by HIV-infected cells or free virus. Surprisingly, the vs loop peptide blocked 75-95% of complement activation on HIV-inf ected cells. While the V3 loop peptide also blocked a substantial port ion of the neutralizing activity in serum from infected persons for fr ee virus it was again more effective in inhibiting complement-mediated effects on free virus. Accordingly, antibody-dependent, complement-me diated virolysis was inhibited by 61-79%. The results of these experim ents indicate that (1) a substantial portion (30-40%) of the antibody in sera from infected persons that is capable of binding to HIV-infect ed cells and HIV virions is V3-specific, and (2) these vs-specific ant ibodies are particularly important for complement activation on infect ed cells and virions. This indicates that the central portion of the V 3 loop, while constituting less than 3% of the amino acid sequence of the HIV envelope, apparently provides a major gp160 site for immune ef fector functions, especially complement activation. (C) 1994 Academic Press, Inc.