Natural killer cells are innate immune cells that control certain microbial infections and tumours. The function of natural killer cells is regulated by a balance between signals transmitted by activating receptors, which recognize ligands on tumours and virus-infected cells, and inhibitory receptors specific for major histocompatibility complex class I molecules. Here, we review the emerging evidence that natural killer cells have an important role in vivo in immune defence.

Here we describe a family of GPI-anchored cell surface proteins that function as ligands for the mouse activating NKG2D receptor. These molecules are encoded by the retinoic acid early inducible (RAE-1) and H60 minor histocompatibility antigen genes on mouse chromosome 10 and show weak homology with MHC class I. Expression of the NKG2D ligands is low or absent on normal, adult tissues; however, they are constitutively expressed on some tumors and upregulated by retinoic acid. Ectopic expression of RAE-1 and H60 confers target susceptibility to NK cell attack. These studies identify a family of ligands for the activating NKG2D receptor on NK and T cells, which may play an important role in innate and adaptive immunity.

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