KLRE/I1 and KLRE/I2: a novel pair of heterodimeric receptors that inversely regulate NK cell cytotoxicity.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Per C SaetherErik Dissen

Abstract

NK cells identify infected, neoplastic, or MHC-disparate target cells via several different receptors. The NK cell receptor KLRE1 lacks known signaling motifs but has nevertheless been shown to regulate NK cell-mediated cytotoxicity. Here we demonstrate that KLRE1 forms functional heterodimers with either KLRI1 or KLRI2. Cotransfection with KLRE1 was necessary for surface expression of the NK cell receptor chains KLRI1 and KLRI2 in 293T cells. Moreover, KLRE1 can be coimmunoprecipitated with KLRI1 or KLRI2 from transfected NK cell lines. By flow cytometry, KLRE1 and KLRI1 showed colinear expression on NK cells, suggesting surface expression as heterodimers. Unlike other killer cell lectin-like receptors, KLRE1/KLRI1 and KLRE1/KLRI2 heterodimers predominantly migrated as single chains in SDS-PAGE, indicating noncovalent association. KLRI1 was coimmunoprecipitated with the tyrosine phosphatase Src homology region 2 domain-containing phosphatase 1. In accordance with an inhibitory function, anti-HA Ab induced reduced killing of FcR-bearing targets by KLRI1-HA-transfected NK cell lines in a redirected cytotoxicity assay. Reciprocally, KLRI2-HA transfectants displayed increased killing in this assay. Finally, Ab to KLRE1 induced inh...Continue Reading

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Citations

Nov 16, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Per C SaetherErik Dissen
Aug 2, 2019·Human Vaccines & Immunotherapeutics·Sarah M BakerLisa A Morici
Aug 8, 2013·European Journal of Immunology·Ana Lobato-PascualMichael R Daws
Feb 17, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lavanya Thiruchelvam-KyleErik Dissen
Jul 18, 2019·Frontiers in Genetics·Jan FutasPetr Horin

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