title: Identification of a cellular ligand for the natural cytotoxicity receptor NKp44.
abstract: With an array of activating and inhibitory receptors, natural killer (NK) cells are involved in the eradication of infected, transformed, and tumor cells. NKp44 is a member of the natural cytotoxicity receptor family, which is exclusively expressed on activated NK cells. Here, we identify natural cytotoxicity receptor NKp44 (NKp44L), a novel isoform of the mixed-lineage leukemia-5 protein, as a cellular ligand for NKp44. Unlike the other MLL family members, NKp44L is excluded from the nucleus, but expressed at the cell-surface level; its subcellular localization is being associated with the presence of a specific C-terminal motif. Strikingly, NKp44L has not been detected on circulating cells isolated from healthy individuals, but it is expressed on a large panel of the tumor and transformed cells. The sharply decreased NK lysis activity induced by anti-NKp44L antibodies directly demonstrates the role of NKp44L in cytotoxicity. Taken together, these results show that NKp44L could be critical for NK cell-mediated innate immunity. The identification and cellular distribution of NKp44L highlight the role of this self-molecule as a danger signal to alert the NK cell network.
authors: Laboratoire Immunité et Infection, Institut National de la Santé et de la Recherche Médicale, UMR-S945.
authors: Florence
authors: F
authors: Baychelier
authors: Alexis
authors: A
authors: Sennepin
authors: Myriam
authors: M
authors: Ermonval
authors: Karim
authors: K
authors: Dorgham
authors: Patrice
authors: P
authors: Debré
authors: Vincent
authors: V
authors: Vieillard
mesh_terms: D020816:Amino Acid Motifs; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D015723:Gene Library; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000235:genetics / Q000276:immunology*; D009928:Organ Specificity; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques
chemical_list: D057134:Antibodies, Neutralizing; D004268:DNA-Binding Proteins; C460660:KMT2E protein, human; D008024:Ligands; D055629:Natural Cytotoxicity Triggering Receptor 2; D020033:Protein Isoforms