Function of CD3 epsilon-mediated signals in T cell development

The T cell antigen receptor (TCR) and pre-TCR complexes are composed of mul tiple signal-transducing subunits (CD3 gamma, CD3 delta, CD3 epsilon, and z eta) that each contain one or more copies of a semiconserved functional mot if, the immunoreceptor tyrosine-based activation motif (ITAM). Although bio chemical studies indicate that individual TCR-ITAMs may bind selectively or with different affinity to various effector molecules, data from other exp eriments suggest that at least some ITAMs are functionally equivalent. In t his study, we examined the role of CD3 epsilon ITAM-mediated signals in T c ell development by genetically reconstituting CD3 epsilon-deficient mice wi th transgenes encoding either wild-type or ITAM-mutant (signaling defective ) forms of the protein. The results demonstrate that signals transduced by CD3 epsilon are not specifically required for T cell maturation but instead contribute quantitatively to TCR signaling in a manner similar to that pre viously observed for zeta chain. Unexpectedly, analysis of TCR-transgenic/C D3 epsilon-mutant mice reveals a potential role for CD3 epsilon signals in T cell survival.