Human monoclonal antibody 98-6 reacts with the fusogenic form of gp41

A mixture of two peptides from gp41 (N36 and C34) forms an or-helical struc ture that is thought to represent the fusogenic form of gp41. A human anti- gp41 monoclonal antibody (mAb 98-6), generated from the cells of an infecte d individual, reacted poorly with C34, but binding was strongly enhanced wh en N36 was added, indicating that the mAb reacts with a conformational epit ope present in the fusogenic structure formed by the interaction of peptide s N36 and C34. The epitope recognized by mAb 98-6 was found in lysates of v irions on oligomeric forms of gp41 (dimers, trimers, and tetramers). On inf ected cells, the epitope was present as oligomers of gp41, as monomers of g p41, and as part of the envelope polyprotein gp160, obtained after biotinyl ation of intact cells, which were then lysed and immunoprecipitated with va rious mAbs. In lysates of infected cells, the epitope was present as part o f both monomeric gp41 and gp160. These studies demonstrate that infected hu mans can respond to the fusogenic form of gp41 and that the anti-gp41 mAb s tudied here recognizes a conformational epitope formed by the interaction o f two regions of gp41, which forms an cu-helical bundle. This epitope is fo und on several forms of gp41 as it occurs in virions, on the surface of inf ected cells, and in infected cells, (C) 2000 Academic Press.