Structural biology of γδ T cell receptors

T cell receptor (TCR) diversity underpins cellular immunity. While αβ TCRs have been extensively studied in the context of major histocompatibility complex (MHC)-restricted antigen recognition, the γδ TCR system remains underexplored. Unlike their αβ counterparts, γδ TCRs display versatile, often MHC-independent recognition modes, engaging diverse ligands ranging from butyrophilins (BTNs) and other disparate molecules. Recent advances in cryo-electron microscopy (cryo-EM) paired with crystallographic data have illuminated critical aspects of γδ TCR -ligand interactions, the CD3 complex architecture, and the inherent flexibility underpinning their varied recognition modes. In this review, we compare the classical αβ TCR-MHC paradigm against the backdrop of emerging γδ TCR structures, highlighting the latest cryo-EM findings and their implications for immunobiology.