title: Autologous and allogeneic HLA KIR ligand environments and activating KIR control KIR NK-cell functions.
abstract: NK-cell function is regulated by a balance between inhibitory and activating killer cell immunoglobulin-like receptors (KIR) that specifically recognize HLA class I molecules. Using KIR-specific mAb to discriminate between KIR2DS1 and KIR2DL1 receptors, we show that KIR2DS1(+) NK cells are C2-alloreactive only from C2(-) individuals. Moreover, using an in vitro model of NK-cell expansion, we show here that the frequency of KIR2DL1(+) NK cells is significantly higher in the absence of C2 ligand on stimulator EBV-B cells than in its presence. This observation was made regardless of the presence or absence of the autologous C2 ligand, suggesting that the C2(-) EBV-B stimulator cells used in this in vitro model could activate unlicensed KIR2DL1(+) NK cells. In the case of KIR2DL1(+)/S1(+) genotyped individuals, KIR2DS1(+) NK-cell frequency was increased after stimulation with C2(+) compared with C2(-) stimulator B cells, but only from C2(-) individuals. Altogether, these data highlight the C2 alloreactivity of KIR2DS1(+) NK cells that is only observed in C2(-) individuals. These results provide new insights into the way in which NK KIR cell expansion might be regulated in an allogeneic environment.
authors.affiliation: Etablissement Français du Sang, Université de Nantes, Nantes Atlantique Universités, Immunovirologie et polymorphisme génétique, EA4271, Nantes, France.
authors.forename: Maelig
authors.initials: M
authors.lastname: Morvan
authors.forename: Gaëlle
authors.initials: G
authors.lastname: David
authors.forename: Véronique
authors.initials: V
authors.lastname: Sébille
authors.forename: Aurore
authors.initials: A
authors.lastname: Perrin
authors.forename: Katia
authors.initials: K
authors.lastname: Gagne
authors.forename: Catherine
authors.initials: C
authors.lastname: Willem
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Kerdudou
authors.forename: Laure
authors.initials: L
authors.lastname: Denis
authors.forename: Béatrice
authors.initials: B
authors.lastname: Clémenceau
authors.forename: Gilles
authors.initials: G
authors.lastname: Folléa
authors.forename: Jean-Denis
authors.initials: JD
authors.lastname: Bignon
authors.forename: Christelle
authors.initials: C
authors.lastname: Retière
mesh_terms: D015551:Autoimmunity / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005838:Genotype; D006680:HLA Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008024:Ligands; D011485:Protein Binding; D054340:Receptors, KIR / Q000276:immunology*
chemical_list: D006680:HLA Antigens; D008024:Ligands; D054340:Receptors, KIR