The effect of prior activation history on subsequent responses of cloned T helper 1 (Thl) cells to TCR-mediated stimuli was examined. Thl cells were maintained by stimulation with IL2 alone or by stimulation with specific antigen and APC in addition to IL2. Cells carried under both conditions proliferated equivalently in responses to anti-CD3 antibody. However, anti-CD3 induced strong phosphatidyl inosotol (PI) hydrolysis and increased [Ca++]i only in cells that had been maintained by stimulation with specific antigen + APC gave neither PI nor Ca++ responses. The signaling pathways utilizing by Thl cells were thus influenced by prior stimulation through the TCR. Signal transduction pathways induced by endogenous superantigen stimulation of T cells were analyzed with both cloned and heterogeneous responding T cells. It was found that both PI hydrolysis and increased [CA++]i were induced by Mls(a) (mtv-7) superantigen-bearing APC. Using TCR transgenic mice it was further demonstrated that in mice expressing Mls(a) as a self antigen, no Mls(a)-specific response was induced in peripheral T cells; in contrast thymocytes did respond to self Mls(a) by conjugate formation and increased [Ca++]i, demonstrated that immature thymocytes, prior to negative selection, respond specifically to self superantigen.
