Molecular mechanisms of T cell co-stimulation and co-inhibition

The central role of co-stimulatory and co-inhibitory receptors in T cell biology has been proven by the effective therapeutic targeting of some of these molecules. However, the molecular aspects of T cell co-stimulation and co-inhibition are far from being fully understood. Here, the authors discuss emerging concepts in T cell co-signalling. Co-stimulatory and co-inhibitory receptors have a pivotal role in T cell biology, as they determine the functional outcome of T cell receptor (TCR) signalling. The classic definition of T cell co-stimulation continues to evolve through the identification of new co-stimulatory and co-inhibitory receptors, the biochemical characterization of their downstream signalling events and the delineation of their immunological functions. Notably, it has been recently appreciated that co-stimulatory and co-inhibitory receptors display great diversity in expression, structure and function, and that their functions are largely context dependent. Here, we focus on some of these emerging concepts and review the mechanisms through which T cell activation, differentiation and function is controlled by co-stimulatory and co-inhibitory receptors.