Identification of the ligands for KLRG1, an inhibitory receptor expressed on NK cells.

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Bodies of the metazoan organisms are protected by the immune system. The immune system of vertebrates consists of acquired and innate immunity. Natural killer (NK) cells play pivotal roles in innate immunity especially against cancer cells and intracellular pathogens. NK cell recognition of targets involves NK cell receptors with opposing functions: inhibitory receptors and activating receptors. Balance of signals from these receptors decides activation of NK cells. Most of the known ligands for the inhibitory NK cell receptors are MHC class I molecules, which are considered as markers of self. However, NK cell recognition of targets is not solely depend on MHC class I. Indeed, NK cells express inhibitory receptors of which ligands are unidentified, which include KLRG1. KLRG1 is a lectin-like inhibitory receptor expressed on subsets of NK and T cells. Expression of KLRG1 is also regulated by infection. In the present study, our group identified three classical cadherins, which contribute to cell-cell adhesion through homotypic interaction, as ligands for KLRG1. We also showed that ligation of KLRG1 by E-cadherin inhibit NK cell ctyotoxocity. Because the classical cadherins that KLRG1 recognizes are distributed ubiquitously among the body, KLRG1 may contribute to the termination of immune response induced by infection. The notion that expression of E-cadherin is often lost or attenuated in malignant carcinoma raises a possibility that KLRG1-expressing NK cells may play a role in malignant tumor surveillance. The current study provides a new concept that cadherins contribute to regulation of immune response through recognition by KLRG1.