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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

Abstract : 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.
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Contributor : Katia Gagne Connect in order to contact the contributor
Submitted on : Monday, September 20, 2021 - 5:08:33 PM
Last modification on : Wednesday, September 22, 2021 - 3:16:22 AM

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Maelig Morvan, Catherine Willem, Katia Gagne, Nolwenn Kerdudou, Gaelle David, et al.. 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. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2009, 182 (11), pp.6727 - 6735. ⟨10.4049/jimmunol.0900212⟩. ⟨inserm-03349757⟩

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