BLOCKED RAS ACTIVATION IN ANERGIC CD4(-CELLS() T)

T cell anergy is a state of functional unresponsiveness characterized by the inability to produce interleukin-2 (IL-2) upon T cell receptor stimulation. The mitogen-activated protein kinases ERK-1 and ERK-2 and the guanosine triphosphate-binding protein p21(Ras) were found to rem ain unactivated upon stimulation of anergic murine T helper cell 1 clo nes. The inability to activate the Ras pathway did not result from a d efect in association among Shc, Grb-2, and murine Son of Sevenless, no r from a defect in their tyrosine phosphorylation. This block in Ras a ctivation may lead to defective transactivation at activator protein 1 sites in anergic cells and may enable T cells to shut down IL-2 produ ction selectively during anergy.