Killer Ig-like receptor ligand mismatch directs NK cell expansion in vitro.
NK cell alloreactivity is governed largely through failure to detect self-HLA class I ligands by the clonally distributed inhibitory killer Ig-like receptors (KIR) expressed on the NK cell surface. In this study, we investigated the extent to which HLA class I-KIR interactions influence human NK cell proliferation in the allogeneic setting. NK cells were cultured with feeder cells either matched or mismatched for inhibitory KIR ligands, the latter lacking one or more ligands present in the NK cell donor. In postculture cytotoxicity assays, the ability of polyclonal NK cells to kill KIR ligand-mismatched targets was enhanced by exposure to appropriately mismatched feeder cells in prior culture. This corresponded with an increased frequency of postculture donor NK cells expressing a given inhibitory KIR if the allogeneic feeder cells used in the culture lacked its ligand. Similar skewing of KIR distribution was seen in clonally expanded NK cells. Finally, a flow cytometry-based proliferation assay was used to show KIR-specific NK cell division in response to missing self. The findings demonstrate that KIR distribution among a population of alloresponding peripheral blood NK cells is shaped by the HLA class I environment.
Rose
Mingus J J
MJ
Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia.
Brooks
Andrew G
AG
Stewart
Lisbeth A
LA
Nguyen
Thi H
TH
Schwarer
Anthony P
AP
D049109:Cell Proliferation; D002478:Cells, Cultured; D002999:Clone Cells; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology; D015235:HLA-B Antigens / Q000378:metabolism / Q000502:physiology; D015236:HLA-C Antigens / Q000378:metabolism / Q000502:physiology; D006650:Histocompatibility Testing; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D054340:Receptors, KIR / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D054349:Receptors, KIR3DS1 / Q000172:deficiency / Q000378:metabolism / Q000502:physiology
D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D015236:HLA-C Antigens; C496212:KIR2DS1 protein, human; C433932:KIR2DS2 protein, human; C541358:KIR2DS3 protein, human; D008024:Ligands; D054340:Receptors, KIR; D054349:Receptors, KIR3DS1