αβ and γδ T cell receptors: Similar but different

There are 2 populations of T lymphocytes, αβ T and γδ T cells, that can be distinguished by the expression of either an αβ TCR or a γδ TCR, respectively. Pairing of the Ag binding heterodimer, which consists of TCR-α/TCR-β (TCRαβ) or TCR-γ/TCR-δ (TCRγδ), with proteins of the CD3 complex forms the complete αβ or γδ TCR. Despite some similarities in the structure of TCRαβ and TCRγδ 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 CD3ε occurs with all activating αβ TCR ligands and is required to induce αβ TCR signaling. In sharp contrast, CD3ε PRS exposure was not induced by binding of those ligands to the γδ TCR that have been studied. Further, signaling by the γδ TCR occurs independently of CD3ε PRS exposure. Interestingly, it can be enhanced by anti-CD3ε Ab-induced enforcement of CD3ε PRS exposure. This review contrasts these two similar, but different immune receptors.