Intercellular traffic of human immunodeficiency virus type 1 transactivator protein defined by monoclonal antibodies

Monoclonal antibodies (mAbs) directed against the amino-terminal region (N- terminal sequence 2-19) of transactivator protein (tat) of HIV-1 have been shown to inhibit intercellular transactivation mediated by the extracellula r tat protein. The intracellular transactivation was not significantly affe cted by anti-tat mAbs, The specificity of anti-tat mAbs in abolishing the t ransactivating potential of extracellular tat is documented by studies with mAbs to HIV-1 reverse transcriptase, or to a human mammary cancer protein. None of these antibodies showed any inhibitory effect on intercellular tra nsactivation, Specific interaction of anti-tat Ige with tat protein express ed in Jurkat cells is further supported by experiments on immunoblotting, E xtracellular tat is responsible for signals which induce a variety of biolo gical responses in HIV-infected cells, as well as in uninfected cells. The fact that anti-tat mAbs can abolish the intercellular traffic of tat protei n offers a unique strategy in the development of vaccines against AIDS. (C) 1999 Federation of European Biochemical Societies.