EXPLORATION OF ANTIGENIC VARIATION IN GP120 FROM CLADES-A THROUGH CLADES-F OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 BY USING MONOCLONAL-ANTIBODIES

The reactivities of a panel of 14 monoclonal antibodies (MAbs) with mo nomeric gp120 derived from 67 isolates of human immunodeficiency virus type 1 of clades A through F were assessed by using an antigen-captur e enzyme-linked immunosorbent assay. The MAbs used were all raised aga inst gp120 or gp120 peptides from clade B viruses and were directed at a range of epitopes relevant to human immunodeficiency virus type 1 n eutralization: the V2 and V3 loops, discontinuous epitopes overlapping the CD4-binding site, and two other discontinuous epitopes. Four of t he five V3 MAbs showed modest cross-reactivity within clade B but very limited reactivity with gp120s from other clades. These reactivity pa tterns are consistent with the known primary sequence requirements for the binding of these MAbs, One V3 human MAb (19b), however, was much more broadly reactive than the others, binding to 19 of 29 clade B and 10 of 12 clade E gp120s. The 19b epitope is confined to the flanks of the V3 loop, and these sequences are relatively conserved in clade B and E viruses. In contrast to the limited reactivity of V3 MAbs, CD4-b inding site MAbs were much more broadly reactive across clades, two of these MAbs (205-46-9 and 21h) being virtually pan-reactive across cla des A through F. Another human MAb (A-32) to a discontinuous epitope w as also pan-reactive. The CD4-binding site is strongly conserved betwe en clades; but when considering the epitopes near the CD4-binding site , clade D gp120 appears to be the most closely related to clade B and clade E appears to be the least related. A tentative rank order for th ese epitopes is B/D-A/C-E/F. V2 MAbs reacted sporadically within and b etween clades, and no clear pattern was observable. While results from binding assays do not predict neutralization serotypes, they suggest that there may be antigenic subtypes related, but not identical, to th e genetic subtypes.