IDENTIFICATION OF A SYNTHETIC PEPTIDE THAT MIMICS AN HIV GLYCOPROTEIN-120 ENVELOPE CONFORMATIONAL DETERMINANT EXPOSED FOLLOWING LIGATION OFGLYCOPROTEIN-120 BY CD4

CD4 ligation of HIV envelope gp120 results in conformational changes i n gp120 that lead to exposure of the gp41 fusogenic domain and fusion with the host cell membrane, One determinant at or near the CD4-bindin g site exposed on gp120 subsequent to CD4 binding is defined by two hu man MAbs termed 17b and 48d, These MAbs do not block CD4 binding to gp 120; rather, their binding to gp120 is upregulated following CD4 bindi ng, To determine if synthetic peptide mimetopes could be found that re flect conformational determinants on the surface of gp120, synthetic g p120 peptides from 10 divergent HIV isolates were screened for their a bility to bind to 17b and 48d in ELISAs, Although MAb 48d binds to HIV IIIB recombinant gp120 protein, in our studies 48d selectively bound only to the HIV Can0A V3 peptide and not to HIV IIIB V3 peptide, where as MAb 17b bound none of the peptides tested, Monoclonal antibody 480 bound to the HIV Can0A V3 peptide both in solid-phase ELISA and in sol ution in a competitive ELISA, but could not bind to HIV Can0A V3 pepti de bound to human T cells, The HIV Can0A V3 peptide induced anti-HIV a ntibodies in rhesus monkeys that neutralized the laboratory-adapted HI V MN strain but did not induce antibodies that neutralized HIV IIIB/LA I, HIV SF-2, or HIV RF isolates, or that neutralized HIV primary isola tes, These data suggested that the primary sequence of the HIV Can0A V 3 loop exists in a conformer that mimicks a non-V3 determinant of nati ve gp120 exposed subsequent to CD4 binding on the surface of gp120 of laboratory-adapted HIV strains, Structural studies of the Can0A V3 pep tide and/or the 48d MAb may provide important information regarding th e nature of gp120 conformational changes that occur following gp120 li gation by CD4.