ANTIGENIC IMPLICATIONS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE QUATERNARY STRUCTURE - OLIGOMER-SPECIFIC AND OLIGOMER-SENSITIVE MONOCLONAL-ANTIBODIES

A majority of monoclonal antibodies (mAbs) raised against soluble olig omeric human immunodeficiency virus type 1 isolate IIIB (HIV-1(IIIB)) envelope (env) glycoprotein reacted with conformational epitopes withi n the gp120 or gp41 subunits. Of 35 mAbs directed against gp41, 21 pre ferentially reacted with oligomeric env. A subset of these mAbs reacte d only with env oligomers (oligomer-specific mAbs). In contrast, only 1 of 27 mAbs directed against the gp120 subunit reacted more strongly with env oligomers than with monomers, and none were oligomer-specific . However, 50% of anti-gp120 mAbs preferentially recognized monomeric env, suggesting that some epitopes in gp120 are partially masked or al tered by intersubunit contacts in the native env oligomer. Two mAbs to oligomer-dependent epitopes in gp41 neutralized HIV-1(IIIB) and HIV-1 (SF2), and binding of these mAbs to env was blocked by preincubation w ith HIV-1-positive human serum. Thus, immunization with soluble, oligo meric env elicits antibodies to conserved, conformational epitopes inc luding a newly defined class of neutralizing antibodies that bind to o ligomer-specific epitopes in gp41, and may also minimize the productio n of antibodies that preferentially react with monomeric env protein.