NK cell-mediated lysis of autologous HCMV-infected skin fibroblasts is highly variable among NK cell clones and polyclonal NK cell lines.
Lysis of human cytomegalovirus (HCMV)-infected fibroblasts by autologous natural killer (NK) cells was examined in vitro. For NK cell clones, receptor expression was determined at the level of mRNA and cell-surface protein and compared to the lysis of HCMV AD169 strain-infected fibroblasts in which HLA class I was >70% downregulated. The clones ranged broadly in their ability to lyse AD169-infected fibroblasts, correlating neither with the expression of inhibitory KIR, leukocyte inhibitory receptor-1, or CD94:NKG2A receptors nor with the number of different inhibitory KIR expressed per clone. Some lines of polyclonal NK cells preferentially lysed AD169-infected cells and similarly lysed fibroblasts infected with mutant virus RV798, which lacks the genes for downregulating HLA class I. These results demonstrate that NK cell lysis of HCMV-infected autologous fibroblasts is more complex than a simple missing-self mechanism involving downregulation of HLA class I and failure to engage inhibitory self-specific KIR.
Carr
William H
WH
Department of Structural Biology, Stanford University, California 94305-5126, USA.
Little
Ann-Margaret
AM
Mocarski
Edward
E
Parham
Peter
P
D002460:Cell Line; D002999:Clone Cells; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D005814:Genes, Viral; D006680:HLA Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D009154:Mutation; D011971:Receptors, Immunologic / Q000378:metabolism; D054340:Receptors, KIR; D012867:Skin / Q000276:immunology / Q000821:virology
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D011971:Receptors, Immunologic; D054340:Receptors, KIR