Molecular Determinants of Target Cell Recognition by Human γδ T Cells

The unique capabilities of gamma-delta (gamma delta) T cells to recognize cells under stressed conditions, particularly infected or transformed cells, and killing them or regulating the immune response against them, paved the way to the development of promising therapeutic strategies for cancer and infectious diseases. From a mechanistic standpoint, numerous studies have unveiled a remarkable flexibility of gamma delta T cells in employing their T cell receptor and/or NK cell receptors for target cell recognition, even if the relevant ligands often remain uncertain. Here, we review the accumulated knowledge on the diverse mechanisms of target cell recognition by gamma delta T cells, focusing on human gamma delta T cells, to provide an integrated perspective of their therapeutic potential in cancer and infectious diseases.