Abstract
Natural killer (NK) cells are innate cytotoxic lymphocytes that specialize in the defense against viral infection and oncogenic transformation. Their action is tightly regulated by signals derived from inhibitory and activating receptors; the later include proteins such as the Natural Cytotoxicity Receptors (NCRs: NKp46, NKp44 and NKp30). Among the NCRs, NKp46 is the only receptor that has a mouse orthologue named Ncr1. NKp46/Ncr1 is also a unique marker expressed on NK and on Lymphoid tissue inducer (LTI) cells and it was implicated in the control of various viral infections, cancer and diabetes. We have previously shown that human NKp46 recognizes viral hemagglutinin (HA) in a sialic acid-dependent manner and that the O-glycosylation is essential for the NKp46 binding to viral HA. Here we studied the molecular interactions between Ncr1 and influenza viruses. We show that Ncr1 recognizes influenza virus in a sialic acid dependent manner and that N-glycosylation is important for this binding. Surprisingly we demonstrate that none of the predicted N-glycosilated residues of Ncr1 are essential for its binding to influenza virus and we thus conclude that other, yet unidentified N-glycosilated residues are responsible for its recognition. We have demonstrated that N glycosylation play little role in the recognition of mouse tumor cell lines and also showed the in-vivo importance of Ncr1 in the control of influenza virus infection by infecting C57BL/6 and BALB/c mice knockout for Ncr1 with influenza.
Highlights
Natural killer (NK) cells are innate cytotoxic lymphocytes that specialize in the defense against viral infection and oncogenic transformation [1,2,3]
We have previously demonstrated that human NKp46 recognizes viral HA in a sialic acid dependent manner and that the recognition of HA by NKp46 is dependent on Oglycosylation of the Threonine residue located in position 225 of
For that purpose we examined the structures of both Ncr1 and NKp46
Summary
Natural killer (NK) cells are innate cytotoxic lymphocytes that specialize in the defense against viral infection and oncogenic transformation [1,2,3] Their activity is tightly regulated by cytokines and by signals derived from inhibitory and activating receptors [1,2,3]. NKp46/Ncr is a unique marker expressed on NK and on Lymphoid tissue inducer (LTI) cells [3] It was implicated in the control of various viral infections [4,5,6], cancers [7,8,9], bacterial infection such as Fusobacterium nucleatum [10] and type I diabetes [11,12]
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