PROBING THE STRUCTURE OF THE V2-DOMAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SURFACE GLYCOPROTEIN GP120 WITH A PANEL OF 8 MONOCLONAL-ANTIBODIES - HUMAN IMMUNE-RESPONSE TO THE V1-DOMAIN AND V2-DOMAIN

We have analyzed a panel of eight murine monoclonal antibodies (MAbs) that depend on the V2 domain for binding to human immunodeficiency vir us type 1 (HIV-1) gp120. Each MAb is sensitive to amino acid changes w ithin V2, and some are affected by substitutions elsewhere. With one e xception, the MAbs were not reactive with peptides from the V2 region, or only poorly so. Hence their ability to bind recombinant strain III B gp120 depended on the preservation of native structure. Three MAbs c ross-reacted with strain RF gp120, but only one cross-reacted with MN gp120, and none bound SF-2 gp120. Four MAbs neutralized HIV-1 IIIB wit h various potencies, and the one able to bind MN gp120 neutralized tha t virus. Peptide serology indicated that antibodies cross-reactive wit h the HxB2 VI and V2 regions are rarely present in HIV-1-positive sera , but the relatively conserved segment between the V1 and V2 loops was recognized by antibodies in a significant fraction of sera. Antibodie s able to block the binding of V2 MAbs to IIIB or MN gp120 rarely exis t in sera from HIV-1-infected humans; more common in these sera are an tibodies that enhance the binding of V2 Mabs to gp120. This enhancemen t effect of HIV-1-positive sera can be mimicked by several human MAbs to different discontinuous gp120 epitopes. Soluble CD4 enhanced bindin g of one V2 MAb to oligomeric gp120 but not to monomeric gp120, perhap s by inducing conformational changes in the oligomer.