Good HLA-I and HLA-II matches do not guarantee rejection-free corneal transplantation. Some corneal transplants fail despite such matches, suggesting that other antigens might be targets for rejection. Major-histocompatibility-complex  class I–related chain A (MICA) antigens are the ligands of NKG2D which is an
activating or coactivating receptor expressed on human NK cells and CD8⁺T cells. MICA was proposed to participate in kidney, heart, liver and pancreas transplantation. We sought to determine whether MICA might play a role in the immune responses of corneal allograft rejection. Here we demonstrate the first
evidence to our knowledge of MICA expression on human corneal epithelium of patients with corneal allograft rejection in vivo. A significant increase in tear levels of soluble MICA was shown in those patients without MICA expression in corneal imprints. MICA expression on corneal epithelium and lower levels of sMICA in tear was associated with visual impairment at 6 months post-rejection. Furthermore, ectopic expression of MICA on corneal epithelium in vitro enhanced the cytotoxicity mediated by NK cells or CD8⁺T cells, which could be blocked by anti-MICA antibody. Our results suggest that MICA molecule may contribute to cytotoxic responses mediated by activated immune effector cells in corneal graft rejection.