Human NK Cell Education by Inhibitory Receptors for MHC Class I

• DOI: 10.1016/j.immuni.2006.06.013
• Publication Date: 2006-08-11T11:09:52Z
• Authors: Nicolas Anfossi; Pascale André; Sophie Guia; Christine S. Falk; Sophie Roetynck; C. Andrew Stewart; Violette Breso; Coralie Frassati; Denis Reviron; Derek Middleton; François Romagné; Sophie Ugolini; Eric Vivier
• Keywords: MESH: Killer Cells, Natural; Heterozygote; [SDV.IMM] Life Sciences [q-bio]/Immunology; Immunology; MESH: Phenotype; MESH: Histocompatibility Antigens Class I; Cell Line; Mice; 03 medical and health sciences; 0302 clinical medicine; Receptors, KIR; Immunology and Allergy; Animals; Humans; MESH: Animals; Receptors, Immunologic; MESH: Mice; MESH: Receptors, Immunologic; MESH: Heterozygote; MESH: Humans; Histocompatibility Antigens Class I; MESH: Cell Line; Killer Cells, Natural; Infectious Diseases; Phenotype; CELLIMMUNO; [SDV.IMM]Life Sciences [q-bio]/Immunology; Receptors, Natural Killer Cell

Natural killer (NK) cells recognize the absence of self MHC class I as a way to discriminate normal cells from cells in distress. In humans, this "missing self" recognition is ensured by inhibitory receptors such as KIR, which dampen NK cell activation upon interaction with their MHC class I ligands. We show here that NK cells lacking inhibitory KIR for self MHC class I molecules are present in human peripheral blood. These cells harbor a mature NK cell phenotype but are hyporesponsive to various stimuli, including MHC class I-deficient target cells. This response is in contrast to NK cells that express a single inhibitory KIR specific for self MHC class I, which are functionally competent when exposed to the same stimuli. These results show the involvement of KIR-MHC class I interactions in the calibration of NK cell effector capacities, suggesting its role in the subsequent "missing self" recognition.