Innate immune recognition by stimulatory immunoreceptors

The specificity of cells of the innate immune system is determined in part by various stimulatory receptors that function in different forms of immune recognition. NKG2D, a stimulatory receptor expressed by natural killer (NK) cells, macrophages and certain T cell subsets, recognizes various families of ‘induced-self’ ligands. The ligands are distantly related to class I MHC molecules and are induced in ‘distressed’ cells as markers of abnormal self. Another form of innate immune recognition is exemplified by the Ly49H receptor, which is expressed by a subset of NK cells. The Ly49H receptor directly recognizes a virus-encoded protein expressed by cells infected with mouse cytomegalovirus (MCMV) and the Ly49h gene is identical to the Cmv1R gene, which confers resistance to MCMV infections. Yet another group of receptors (the triggering receptors expressed by myeloid cells, or TREMs), which are exclusively expressed by myeloid cells, have been shown to amplify cytokine responses to bacterial products and have also been implicated in the pathogenesis of septic shock.