| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
We asked whether the antibodies against two distinct extracellular _-helical regions of gp41 (DP107 and DP178) of human immunodeficiency virus type 1 have any relevance to clinical progressions. Anti-DP107 titers steadily declined as the disease progress. The decrease was statistically associated with the increase of vital load or the decrease of T cell numbers but not with the changes of B or NK cell numbers. In contrast, the antibodies against DP178 and gp41 remained elevated during the entire clinical course. A mixture of two peptides from gp41 (N36 and C34) forms an _-helical structure that is thought to represent the fusion active core of gp41. A human monoclonal anti-gp41 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 fusion active core structure formed by the interaction of peptides N36 and C34. The epitope recognized by mAb 98-6 was found in 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. In infected cells, the epitope was present as part of both monomeric gp41 and gp160. These studies demonstrate that infected humans can respond to the fusion active 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 form an _-helical bundle. This epitope is found on several forms of gp41 as they occur in virions, on the surface of infected cells, and in infected cells.
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