Autologous and allogeneic HLA KIR ligand environments and activating KIR control KIR NK-cell functions.
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.
Morvan
Maelig
M
Etablissement Français du Sang, Université de Nantes, Nantes Atlantique Universités, Immunovirologie et polymorphisme génétique, EA4271, Nantes, France.
David
Gaëlle
G
Sébille
Véronique
V
Perrin
Aurore
A
Gagne
Katia
K
Willem
Catherine
C
Kerdudou
Nolwenn
N
Denis
Laure
L
Clémenceau
Béatrice
B
Folléa
Gilles
G
Bignon
Jean-Denis
JD
Retière
Christelle
C
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*
D006680:HLA Antigens; D008024:Ligands; D054340:Receptors, KIR