γδ T cell surveillance via CD1 molecules

gamma delta T cells are a prominent epithelial-resident lymphocyte population, possessing multi-functional capacities in the repair of host tissue, pathogen clearance, and tumor surveillance. Although three decades have now passed since their discovery, the nature of gamma delta T cell receptor (TCR)-mediated ligand recognition remains poorly defined. Recent studies have provided structural insight into this recognition, demonstrating that gamma delta T cells survey both CD1 and the presented lipid, and in some cases are exquisitely lipid specific. We review these findings here, examining the molecular basis for and the functional relevance of this interaction. We discuss potential implications on the notion that non-classical major histocompatibility complex (MHC) molecules may function as important restricting elements of gamma delta TCR specificity, and on our understanding of gamma delta T cell activation and function.