Cattle MIC is a ligand for the activating NK cell receptor NKG2D

Major histocompatibility complex (MHC) class I chain-related (MIC) genes encode molecules that are expressed in response to stress, signalling immune system cells primarily via the activating receptor NKG2D. We investigated the expression of receptors for MIC in lymphocyte subsets found in peripheral blood, lymph node and gut in cattle and demonstrated their presence on natural killer (NK) cells, γδ T cells and CD8+ T cells. Recognition of MIC by NKG2D was formally demonstrated using recombinant protein and an ELISA. Staining with a cross-reactive monoclonal antibody recognising both human and cattle MIC showed that MIC is constitutively expressed within cattle intestinal epithelium. A functional response to soluble MIC was observed in receptor-bearing cells in blood, lymph node and gut, the latter requiring relatively high levels of MIC to trigger a response. Results suggest that NKG2D is a functionally important activating receptor in cattle.