One of the most exciting fields in modern medicine is immunotherapy, treatment which looks to harness the power of the immune system to fight disease. A particularly effective strategy uses antibodies designed to influence the activity levels of the immune system. Here we look at two receptors - TIGIT and DNAM-1 - which bind the same ligands but have opposite effects on immune cells, earning them the label `paired receptors'. Importantly, natural killer cells and cytotoxic T cells express both of these receptors, and in certain cases their effector functions are dictated by TIGIT or DNAM-1 signaling. Agonist and antagonist antibodies targeting either TIGIT or DNAM-1 present many therapeutic options for diseases spanning from cancer to auto-immunity. In this review we present cases in which the modulation of these receptors holds potential for the development of novel therapies.
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