MHC class I chain-related genes MICA and MICB are transmembrane glycoproteins that function as ligands for human NKG2D. The two proteins are highly related, sharing 85% amino acid identity, but are also polymorphic. Recognition of MICA or MICB by NKG2D results in the activation of NK cell cytolytic activity and/or cytokine production. MICA/B are minimally expressed on normal cells, but are frequently expressed on or shed from epithelial tumors and can be induced by bacterial and viral infections. MICA and MICB recognition is involved in tumor surveillance, viral infections, and autoimmune diseases.