Different roles for the FcεRI γ chain as a function of the receptor context

Abstract

The high affinity immunoglobulin E receptor (FcεRI) and the B and T cell antigen receptors (TCR) are multimeric complexes containing subunits with cytoplasmic antigen recognition activation motifs (ARAMs). The presence of multiple motifs may be a way to amplify a single signal or provide independent activation modules. Here we have compared the signaling capacity of the same FcεRI γ motif in the context of two different receptors, FcεRI and TCR/CD3, simultaneously reconstituted on the surface of the same ζ- deficient T cell line. Both reconstituted receptors mediate early (phosphorylation) and late (interleukin [IL]-2 release) signals. Mutation of the two tyrosine residues of ARAM γ alters early signaling by both receptors, but the set of substrates phosphorylated via ARAM γ is different for each receptor and is thus dependent on the receptor context. Furthermore, the mutations prevent FċRI- but not TCR/CD3-mediated IL-2 release. These data demonstrate that ARAM γ is necessary for allowing both receptors to phosphorylate the complete set of substrates, and that the CD3 complex, unlike the FċRI β chain, contains activation modules capable of compensating for the absence of a functional ARAM γ in generating late signals such as IL-2 release.