Phenotypic and functional analyses of KIR3DL1+ and KIR3DS1+ NK cell subsets demonstrate differential regulation by Bw4 molecules and induced KIR3DS1 expression on stimulated NK cells.
Recently, the Z27 mAb was shown to recognize the NK cell-activating receptor KIR3DS1, and several genetic studies suggest that the most probable ligands of KIR3DS1 are HLA class I molecules with the Bw4 motif. Despite these findings, the attempts to establish a functional interaction between KIR3DS1 and its potential ligand have been unsuccessful. Here, we study the proliferation and cytotoxicity of KIR3DS1(+) NK cells, compared with KIR3DL1(+) NK cells, according to the Bw4(+) or Bw4(-) allogeneic environment. Our results show for the first time that KIR3DS1 expression on NK cells can be induced after exposure to stimulator cells (221, K562, EBV-B cell lines, and B cells), polyinosinic-polycytidylic acid, IL-15, or IL-2. Furthermore, whereas KIR3DL1(+) NK cell proliferation and cytotoxicity were inhibited in a Bw4(+) but not a Bw4(-) context, KIR3DS1(+) NK cell functions were not influenced by the presence of Bw4 on target cells. Nevertheless, despite the absence of demonstrated regulation of KIR3DS1(+) NK cell functions by HLA-Bw4 molecules, we found a higher KIR3DS1(+) NK cell frequency and higher levels of KIR3DS1 expression in Bw4(+) compared with Bw4(-) individuals. Altogether, these results suggest that KIR3DS1 does not recognize HLA-Bw4 molecules in a physiological context, and they highlight the induced expression of KIR3DS1 observed on stimulated NK cells and the higher frequency of KIR3DS1(+) NK cells in Bw4(+) individuals. Because a protective KIR3DS1-Bw4 association has been reported in viral infections, our results further the understanding of the role of KIR3DS1(+) NK cells in controlling viral infections.
Morvan
Maelig
M
Etablissement Français du Sang, Université de Nantes, ImmunoVirologie et Polymorphisme Génétique, Nantes, France.
Willem
Catherine
C
Gagne
Katia
K
Kerdudou
Nolwenn
N
David
Gaelle
G
Sébille
Véronique
V
Folléa
Gilles
G
Bignon
Jean-Denis
JD
Retière
Christelle
C
D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation / Q000276:immunology; D015235:HLA-B Antigens / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D008213:Lymphocyte Activation; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*; D054341:Receptors, KIR3DL1 / Q000032:analysis*; D054349:Receptors, KIR3DS1 / Q000032:analysis*; D016176:T-Lymphocyte Subsets
D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1