γδ T Cells Link Innate and Adaptive Immune Responses

While most T cells use a CD3-associated α/β T cell receptor as antigen recognition structure, a second population of T cells expresses the alternative γ/δ T cell receptor. γ/δ T cells are a minor population in the peripheral blood but constitute a major population among intestinal intraepithelial lymphocytes. Most γ/δ T cells recognize ligands which are fundamentally different from the short peptides that are seen by α/β T cells in the context of MHC class I or class II molecules. Thus, human Vδ2 T cells recognize small bacterial phosphoantigens, alkylamines and synthetic aminobisphosphonates, whereas Vδ1 T cells recognize stress-inducible MHC-related molecules MICA/B as well as several other ligands. At the functional level, γ/δ T cells rapidly produce a variety of cytokines and usually exert potent cytotoxic activity, also towards many tumor cells. In this article, we discuss the role of γ/δ T cells as a bridge between the innate and the adaptive immune system, based on the interpretation that γ/δ T cells use their T cell receptor as a pattern recognition receptor. Our increasing understanding of the ligand recognition and activation mechanisms of γ/δ T cells also opens new perspectives for the development of γ/δ T cell-based immunotherapies.