2026-06-26T20:12:29Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/970152025-03-18T13:40:07Zcom_20.500.14352_14col_20.500.14352_15

Antón Hurtado, Olga María Vielkind, Susina Peterson, Mary Tagaya, Yutaka Long, Eric 2024-01-31T11:11:19Z 2024-01-31T11:11:19Z 2015 Olga M. Anton, Susina Vielkind, Mary E. Peterson, Yutaka Tagaya, Eric O. Long; NK Cell Proliferation Induced by IL-15 Transpresentation Is Negatively Regulated by Inhibitory Receptors. J Immunol 15 November 2015; 195 (10): 4810–4821. https://doi.org/10.4049/jimmunol.1500414 0022-1767 10.4049/jimmunol.1500414 https://hdl.handle.net/20.500.14352/97015 1550-6606 https://doi.org/10.4049/jimmunol.1500414 IL-15 bound to the IL-15Rα–chain (IL-15Rα) is presented in trans to cells bearing the IL-2Rβ–chain and common γ-chain. As IL-15 transpresentation occurs in the context of cell-to-cell contacts, it has the potential for regulation by and of other receptor–ligand interactions. In this study, human NK cells were tested for the sensitivity of IL-15 transpresentation to inhibitory receptors. Human cells expressing HLA class I ligands for inhibitory receptors KIR2DL1, KIR2DL2/3, or CD94-NKG2A were transfected with IL-15Rα. Proliferation of primary NK cells in response to transpresented IL-15 was reduced by engagement of either KIR2DL1 or KIR2DL2/3 by cognate HLA-C ligands. Inhibitory KIR–HLA-C interactions did not reduce the proliferation induced by soluble IL-15. Therefore, transpresentation of IL-15 is subject to downregulation by MHC class I–specific inhibitory receptors. Similarly, proliferation of the NKG2A+ cell line NKL induced by IL-15 transpresentation was inhibited by HLA-E. Coengagement of inhibitory receptors, either KIR2DL1 or CD94-NKG2A, did not inhibit phosphorylation of Stat5 but inhibited selectively phosphorylation of Akt and S6 ribosomal protein. IL-15Rα was not excluded from, but was evenly distributed across, inhibitory synapses. These findings demonstrate a novel mechanism to attenuate IL-15–dependent NK cell proliferation and suggest that inhibitory NK cell receptors contribute to NK cell homeostasis. eng open access NK Cell Proliferation Induced by IL-15 Transpresentation Is Negatively Regulated by Inhibitory Receptors journal article