The TCR zeta-chain immunoreceptor tyrosine-based activation motifs are sufficient for the activation and differentiation of primary T lymphocytes

The TCR complex signals through a set of 10 intracytoplasmic motifs, termed immunoreceptor tyrosine-based activation motifs (ITAMs), contained within the gamma-, delta-, epsilon-, and zeta-chains. The need for this number of ITAMs is uncertain. Limited and contradictory studies have examined the abi lity of subsets of the TCR's ITAMs to signal into postthymic primary T lymp hocytes. To study signaling by a restricted set of ITAMs, we expressed in t ransgenic mice a chimeric construct containing the IA(s) class II MHC extra cellular and transmembrane domains linked to the cytoplasmic domain of the TCR zeta-chain. Tyrosine phosphorylation and receptor cocapping studies ind icate that this chimeric receptor signals T cells independently of the rema inder of the TCR, We show that CD4(+) and CD8(+) primary T cells, as well a s naive and memory T cells, are fully responsive to stimulation through the IA(s)-zeta receptor. Further, IA(s)-zeta stimulation can induce primary T cell differentiation into CTL, Th1, and Th2 type cells. These results show that the zeta-chain ITAMs, in the absence of the gamma, delta, and epsilon ITAMs, are sufficient for the activation and functional maturation of prima ry T lymphocytes, It also supports the isolated use of the zeta-chain ITAMs in the development of surrogate TCRs for therapeutic purposes.