Abstract

Abstract 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 ζ-chain, the first nonmammalian homologue identified. The comparison of mammalian and chicken ζ proteins revealed high identity of the transmembrane and the C-terminal cytoplasmic domains. Transfection of a mouse ζ-deficient cell line, with the chicken ζ gene, restored surface expression of the murine TCR/CD3 complex. The chicken ζ-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 ζ-chain as a structural and signaling component over a period of 300 million years.

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