The chicken TCR zeta-chain restores the function of a mouse T cell hybridoma

The TCR/CD3 complex has been intensively studied in mammals, but it has been difficult to isolate homologues in other vertebrates. Here, we characterize the chicken zeta-chain, the first nonmammalian homologue identified. The comparison of mammalian and chicken zeta proteins revealed high identity of the transmembrane and the C-terminal cytoplasmic domains. Transfection of a mouse zeta-deficient cell line, with the chicken zeta gene, restored surface expression of the murine TCR/CD3 complex. The chicken zeta-chain was stably associated with the mouse TCR/CD3 components and fully restored its signaling capacity upon stimulation with Ab, superantigen, and peptide Ag. This is the first report of a nonmammalian TCR component that is capable of fully restoring a mammalian TCR in every aspect analyzed, thus demonstrating the enormous selective pressure to maintain the zeta-chain as a structural and signaling component over a period of 300 million years.