T-CELL AND BASOPHIL ACTIVATION THROUGH THE CYTOPLASMIC TAIL OF T-CELL-RECEPTOR ZETA-FAMILY PROTEINS

The zeta-chain of the T-cell antigen receptor is the prototype of a family of proteins that exist as disulfide-linked dimers and are subunits of the T-cell antigen receptor and both IgE and IgG binding Fc receptors. Two related genes encode the zeta and gamma-proteins. In this study we examine the ability of chimeric proteins consisting of the extracellular domain of the alpha-chain of the interleukin 2 receptor (Tac) and the cytoplasmic domain of either zeta or gamma to activate cells when expressed in either T cells or rat basophilic leukemia cells. The zeta and gamma-chimera were effective at eliciting interleukin 2 production in T cells and serotonin release in rat basophilic leukemia cells when externally cross-linked. Cytoplasmic-tail deletion mutants of zeta and gamma were constructed and used to verify the specificity of cell activation by these chimeric proteins. Signaling potencies of complementary mutants having the zeta-tail truncated in position 108 or deleted from positions 66 through 114 suggested the presence of several functional domains in zeta.