The inhibitory receptor NKG2A determines lysis of vaccinia virus-infected autologous targets by NK cells.
Signals transduced by inhibitory receptors that recognize self-MHC class I molecules prevent NK cells from being activated by autologous healthy target cells. In order for NK cells to be activated upon contact with an infected cell, the balance between the activating and inhibitory signals that regulate NK cell function must be altered in favor of activation. By studying liver-derived NK cells, we show that only a subpopulation of NK cells expressing high levels of the inhibitory receptor NKG2A are able to lyse autologous vaccinia-infected targets, and that this is due to selective down-regulation of HLA-E. These data demonstrate that release from an inhibitory receptor:ligand interaction is one mechanism that permits NK cell recognition of a virally infected target, and that the variegated expression of inhibitory receptors in humans generates a repertoire of NK cells with different antiviral potentials.
Brooks
Collin R
CR
The School of Medicine, Southampton University, Southampton, United Kingdom.
Elliott
Tim
T
Parham
Peter
P
Khakoo
Salim I
SI
D001483:Base Sequence; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000235:genetics; D015536:Down-Regulation; D006680:HLA Antigens / Q000378:metabolism; D015234:HLA-A Antigens / Q000235:genetics; D015788:HLA-A1 Antigen; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D008024:Ligands; D008099:Liver / Q000166:cytology / Q000276:immunology; D055654:NK Cell Lectin-Like Receptor Subfamily C; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D054340:Receptors, KIR; D055607:Receptors, Natural Killer Cell; D015398:Signal Transduction; D014162:Transfection; D014616:Vaccinia virus / Q000276:immunology*; D000097625:HLA-E Antigens
D004247:DNA; D006680:HLA Antigens; D015234:HLA-A Antigens; D015788:HLA-A1 Antigen; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D055654:NK Cell Lectin-Like Receptor Subfamily C; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens; C506470:HLA-A*01:01 antigen; C527054:KLRC1 protein, human