γδ T cell responses: How many ligands will it take till we know?

gamma delta T cells constitute a sizeable and non-redundant fraction of the total T cell pool in all jawed vertebrates, but in contrast to conventional alpha beta T cells they are not restricted by classical MHC molecules. Progress in our understanding of the role of gamma delta T cells in the immune system has been hampered, and is being hampered, by the considerable lack of knowledge regarding the antigens gamma delta T cells respond to. The past few years have seen a wealth of data regarding the TCR repertoires of distinct gamma delta T cell populations and a growing list of confirmed and proposed molecules that are recognised by gamma delta T cells in different species. Yet, the physiological contexts underlying the often restricted TCR usage and the chemical diversity of gamma delta T cell ligands remain largely unclear, and only few structural studies have confirmed direct ligand recognition by the TCR. We here review the latest progress in the identification and validation of putative gamma delta T cell ligands and discuss the implications of such findings for gamma delta T cell responses in health and disease. (C) 2017 The Authors. Published by Elsevier Ltd.