THE CYTOPLASMIC DOMAIN OF THE T-CELL RECEPTOR ZETA-CHAIN IS SUFFICIENT TO COUPLE TO RECEPTOR-ASSOCIATED SIGNAL TRANSDUCTION PATHWAYS

The function of the T cell antigen receptor (TCR) invariant chains, CD3-gamma, delta, epsilon, and zeta, is poorly understood. Evidence suggests that CD3 couples receptor ligand binding to intracellular signaling events. To examine the role of the CD3-zeta-chain in TCR-mediated signal transduction, a chimeric protein linking the extracellular and transmembrane domains of CD8 to the cytoplasmic domain of the zeta-chain was constructed. The CD8/zeta-chimera is expressed independently of the TCR and is capable of transducing signals that, by criteria of early and late activation, are indistinguishable from those generated by the intact TCR. These data indicate that CD8/zeta can activate the appropriate signal transduction pathways in the absence of CD3-gamma, delta, and epsilon, and suggest that the role of CD3-zeta is to couple the TCR to intracellular signal transduction mechanisms.