Human Monoclonal Antibody 98-6 Reacts with the Fusogenic Form of gp41

Abstract A mixture of two peptides from gp41 (N36 and C34) forms an α-helical structure 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 infected individual, reacted poorly with C34, but binding was strongly enhanced when N36 was added, indicating that the mAb reacts with a conformational epitope present in the fusogenic structure formed by the interaction of peptides N36 and C34. The epitope recognized by mAb 98-6 was found in lysates of virions on oligomeric forms of gp41 (dimers, trimers, and tetramers). On infected cells, the epitope was present as oligomers of gp41, as monomers of gp41, and as part of the envelope polyprotein gp160, obtained after biotinylation of intact cells, which were then lysed and immunoprecipitated with various mAbs. In lysates of infected cells, the epitope was present as part of both monomeric gp41 and gp160. These studies demonstrate that infected humans can respond to the fusogenic form of gp41 and that the anti-gp41 mAb studied here recognizes a conformational epitope formed by the interaction of two regions of gp41, which forms an α-helical bundle. This epitope is found on several forms of gp41 as it occurs in virions, on the surface of infected cells, and in infected cells.