The enigmatic specificity of gamma delta T cells

In most scientific investigations, the study of mechanism follows the study of function. For example, alpha beta T cells were shown to be important mediators of immunity before the interaction between the T cell receptor (TCR) and peptide-MHC complexes was understood. However, sometimes the study of function follows from the study of mechanism. Research of gamma delta T cell receptors falls into this category. The gamma chain of the TCR was first cloned in 1984, which then led to the discovery of gamma delta T cells in 1985. Since then, research has focused on understanding ligands of the gamma delta TCR with the hope of better understanding the function of gamma delta T cells. An initial assumption was that gamma delta T cells, like alpha beta T cells, recognize peptides bound to MHC molecules; however, recent data indicate that gamma delta T cells are not biased towards MHC recognition in the same way as alpha beta T cells. Although there are intriguing new insights, the specificity and function of gamma delta T cells remains a mystery.