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T cell-dependent immunity commences with T-cell antigen receptor (TCR-CD3) signalling. TCR-CD3 features unique ligand recognition, signalling modalities and convoluted quaternary structure, diverging considerably from “classic”, evolutionary ancient membrane receptors of simpler molecular design and univocal relationship to ligands. TCR-CD3 recognises with exceptional sensorial and discriminatory ability antigens of varying structure, quantity and detection context. Given such a complexity, it is perhaps unsurprising that controversy exists on how TCR-CD3 works. I will report new data suggesting an allosteric mechanism by which TCR-CD3 transmits signals across the plasma membrane that should improve our understanding of how T cell activation begins.
