LCK-INDEPENDENT INHIBITION OF T-CELL ANTIGEN RESPONSE BY THE HIV GP120

Binding of the HIV envelope glycoprotein gp120 to CD4 inhibits T cell activation. We have used a murine T cell clone transfected with either wild-type human CD4 or mutated forms of CD4 to characterize the pathw ays involved in this inhibitory effect of gp120. Ag-induced proliferat ion of T cell clones transfected with human CD4 was completely inhibit ed in the presence of gp120, even though stimulation of this clone is independent of a CD4/MHC class II interaction. In addition, our result s demonstrate that the inhibition by gp120 is not due to the sequestra tion of lck from TCR and does not require activation of lck by gp120. This suggests that CD4 can regulate the initiation of T cell activatio n independently of its interaction with lck. Moreover, we demonstrate that the nonresponsiveness induced by gp120 can be reversed by soluble CD4 when added early after onset of stimulation and that gp120 exerts its inhibitory effect when cells are in the G(0) greater than or equa l to 1 phase of the cell cycle.