T cell receptor signaling for γδT cell development

T cells are central to the vertebrate immune system. Two distinct types of T cells, alpha beta T and gamma delta T cells, express different types of T cell antigen receptors (TCRs), alpha beta TCR and gamma delta TCR, respectively, that are composed of different sets of somatically rearranged TCR chains and CD3 subunits. gamma delta T cells have recently attracted considerable attention due to their ability to produce abundant cytokines and versatile roles in host defense, tissue regeneration, inflammation, and autoimmune diseases. Both alpha beta T and gamma delta T cells develop in the thymus. Unlike the development of alpha beta T cells, which depends on alpha beta TCR-mediated positive and negative selection, the development of gamma delta T cells, including the requirement of gamma delta TCR, has been less well understood. alpha beta T cells differentiate into effector cells in the peripheral tissues, whereas gamma delta T cells acquire effector functions during their development in the thymus. In this review, we will discuss the current state of knowledge of the molecular mechanism of TCR signal transduction and its role in the thymic development of gamma delta T cells, particularly highlighting a newly discovered mechanism that controls proinflammatory gamma delta T cell development.