Mechanisms contributing to T cell receptor signaling and assembly revealedby the solution structure of an ectodomain fragment of the CD3 epsilon gamma heterodimer

The T cell receptor (TCR) consists of genetically diverse disulfide-linked ru and beta chains in noncovalent association with the invariant CD3 subuni ts. CD3 epsilon and CD3 gamma are integral components of both the TCR and p re-TCR. Here, we present the solution structure of a heterodimeric CD3 epsi lon gamma ectodomain complex. A unique side-to-side hydrophobic interface b etween the two C2-set immunoglobulin-like domains and parallel pairing of t heir respective C-terminal beta strands are revealed. Mutational analysis c onfirms the importance of the distinctive linkage as well as the membrane p roximal stalk motif (RxCxxCxE) for domain-domain association. These biochem ical and structural analyses offer insights into the modular pairwise assoc iation of CD3 invariant chains. More importantly, the findings suggest how the rigidified CD3 elements participate in TCR-based signal transduction.