Expression, function, and molecular properties of the killer receptor Ncr1-Noé

Ariella Glasner, Hrvoje Simic, Karmela Miklić, Ziv Roth, Orit Berhani, Isam Khalaila, Stipan Jonjic, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

NK cells kill various cells using activating receptors, such as the natural cytotoxicity receptors (NCRs). NKp46 is a major NCR and is the only NCR expressed in mice (denoted Ncr1). Using Ncr1-deficient mice (Ncr1gfp/pfp) we demonstrated that Ncr1 controls various pathologies, and that in its absence Ncr1-related functions are impaired. In 2012, another Ncr1-related mouse was generated, named Noé, in which a random mutation, W32R, in position 32, impaired the Ncr1-Noé cell surface expression. Interestingly, in the Noé mice, Ncr1-dependent deficiencies were not observed. Additionally, the Noé-NK cells were hyperactivated, probably due to increased Helios expression, and the Noé mice demonstrate increased clearance of influenza and murine CMV. In contrast, in the Ncr1gfp/pfp mice infection with influenza was lethal and we show in the present study no difference in murine CMV infection between Ncr1gfp/pfp and wild-type (WT) mice. Because the foremost difference between the Noé and Ncr1gfp/gfp mice is the presence of a mutated Ncr1-Noé protein, we studied its properties. We show that Ncr1-Noé and various other Ncr1 mutants in position 32 can be expressed on the surface, albeit slowly and unstably, and that ligand recognition and function of the various Ncr1-Noé is similar to the WT Ncr1. We further show that the glycosylation pattern of Ncr1-Noé is aberrant, that the Ncr1-Noé proteins accumulate in the endoplasmic reticulum, and that the expression of Ncr1-Noé proteins, but not WT Ncr1, leads to increased Helios expression. Thus, we suggest that the NK hyperactivated phenotype observed in the Noé mice might result from the presence of the Ncr1-Noé protein.

Original languageAmerican English
Pages (from-to)3959-3969
Number of pages11
JournalJournal of Immunology
Volume195
Issue number8
DOIs
StatePublished - 15 Oct 2015

Bibliographical note

Publisher Copyright:
Copyright © 2015 by The American Association of Immunologists, Inc.

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