TCRγδ cells: Mysterious cells of the immune system

γδ cells participate in pathogenic infections and autoimmune conditions, yet, almost a decade after their discovery, little is known regarding their TCR repertoire or effector functions. Unlike MHC-restricted antigen recognition employed by TCRαβ cells, TCRγδ cells can recognize whole unprocessed antigens in an MHC-independent manner. The nature of positive and negative selection used to shape the repertoire of TCRγδ cells is unclear, especially in the nonlymphoid tissues where these cells predominate. While TCRγδ cells express an activated phenotype and are present in pathological conditions, their roles in immunological protection is unknown. This review will focus on our efforts to study these issues of TCRγδ biology.