αβ and γδ T cell receptors: Similar but different

There are 2 populations of T lymphocytes, alpha beta T and gamma delta T cells, that can be distinguished by the expression of either an alpha beta TCR or a gamma delta TCR, respectively. Pairing of the Ag binding heterodimer, which consists of TCR-alpha/TCR-beta (TCR alpha beta) or TCR-gamma/TCR-delta (TCR gamma delta), with proteins of the CD3 complex forms the complete alpha beta or gamma delta TCR. Despite some similarities in the structure of TCR alpha beta and TCR gamma delta and the shared subunits of the CD3 complex, the 2 receptors differ in important aspects. These include the assembly geometry of the complex, the glycosylation pattern, the plasma membrane organization, as well as the accessibility of signaling motifs in the CD3 intracellular tails. These differences are reflected in the different demands and outcomes of ligand-induced signaling. It was shown that exposure of the proline-rich sequence (PRS) in CD3 epsilon occurs with all activating alpha beta TCR ligands and is required to induce alpha beta TCR signaling. In sharp contrast, CD3 epsilon PRS exposure was not induced by binding of those ligands to the gamma delta TCR that have been studied. Further, signaling by the gamma delta TCR occurs independently of CD3 epsilon PRS exposure. Interestingly, it can be enhanced by anti-CD3 epsilon Ab-induced enforcement of CD3 epsilon PRS exposure. This review contrasts these two similar, but different immune receptors.