Deconstructing the Form and Function of the TCR/CD3 Complex

When T cells encounter antigens via the T cell antigen receptor (TCR), information about the quantity and quality of antigen engagement is relayed to the intracellular signal transduction machinery. This process is poorly understood. The TCR itself lacks a significant intracellular domain. Instead, it is associated with CD3 molecules that contain intracellular signaling domains that couple the TCR/CD3 complex to the downstream signaling machinery. The earliest events in TCR signaling must involve the transfer of information from the antigen binding TCR subunit to the CD3 signaling subunits of the TCR/CD3 complex. Elucidating the structural organization of the TCR with the associated CD3 signaling molecules is necessary for understanding the mechanism by which TCR engagement is coupled to activation. Here, we review the current state of our understanding of the structure and organization of the TCR/CD3 complex.