Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA

Stress-inducible MICA, a distant homolog of major histocompatibility complex (MHC) class I, functions as an antigen for gamma delta T cells and is frequently expressed in epithelial tumors. A receptor for MICA was detected on most gamma delta T cells, CD8(+) alpha beta T cells, and natural killer (NK) cells and was identified as NKG2D. Effector cells from all these subsets could be stimulated by ligation of NKG2D. Engagement of NKG2D activated cytolytic responses of gamma delta T cells and NK cells against transfectants and epithelial tumor cells expressing MICA. These results define an activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses.