Human NK cell education by inhibitory receptors for MHC class I.
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.
Anfossi
Nicolas
N
Innate-Pharma, 13009 Marseille, France.
André
Pascale
P
Guia
Sophie
S
Falk
Christine S
CS
Roetynck
Sophie
S
Stewart
C Andrew
CA
Breso
Violette
V
Frassati
Coralie
C
Reviron
Denis
D
Middleton
Derek
D
Romagné
François
F
Ugolini
Sophie
S
Vivier
Eric
E
D000818:Animals; D002460:Cell Line; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D010641:Phenotype; D011971:Receptors, Immunologic / Q000276:immunology*; D054340:Receptors, KIR; D055607:Receptors, Natural Killer Cell
D015395:Histocompatibility Antigens Class I; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D055607:Receptors, Natural Killer Cell