Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity.
Circulating human natural killer (NK) lymphocytes have been functionally defined by their ability to exert cytotoxic activity against MHC class I-negative target cell lines, including K562. Therefore, it was proposed that NK cells recognized the "missing self." We show here that the Ig-like CD160 receptor expressed by circulating CD56(dim+) NK cells or IL-2-deprived NK cell lines is mainly involved in their cytotoxic activity against K562 target cells. Further, we report that HLA-C molecules that are constitutively expressed by K562 trigger NK cell lysis through CD160 receptor engagement. In addition, we demonstrate, with recombinant soluble HLA-Cw3 and CD160 proteins, direct interaction of these molecules. We also find that CD158b inhibitory receptors partially interfere with CD160-mediated cytotoxicity, whereas CD94CD159a and CD85j have no effect on engagement with their respective ligands. Thus, CD160HLA-C interaction constitutes a unique pathway to trigger NK cell cytotoxic activity.
Le Bouteiller
Philippe
P
Institut National de la Santé et de la Recherche Médicale U563, Hôpital Purpan, 31059 Toulouse Cedex 3, France.
Barakonyi
Aliz
A
Giustiniani
Jérome
J
Lenfant
Françoise
F
Marie-Cardine
Anne
A
Aguerre-Girr
Maryse
M
Rabot
Magali
M
Hilgert
Ivan
I
Mami-Chouaib
Fathia
F
Tabiasco
Julie
J
Boumsell
Laurence
L
Bensussan
Armand
A
D015703:Antigens, CD / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D058851:GPI-Linked Proteins; D015236:HLA-C Antigens / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000502:physiology*; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3
D015703:Antigens, CD; C114505:CD160 protein, human; D058851:GPI-Linked Proteins; D015236:HLA-C Antigens; D007376:Interleukin-2; D037181:Lectins, C-Type; D008565:Membrane Proteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3