title: Reduced KIR2DL1 recognition of MHC class I molecules presenting phosphorylated peptides.
abstract: As initially described by K. Karre and colleagues in the missing self hypothesis, cells expressing self-MHC class I proteins are protected from NK cells attack. In contrast, reduction in the expression of MHC class I molecules due to viral infection or tumor transformation result in the killing of these "abnormal" cells by NK cells via NK-activating receptors. Thus, NK killing of target cells is determined by both negative signals coming from MHC class I proteins and by positive signals derived from the activating ligands. The bound peptide in MHC class I play an important role in the balanced recognition of NK cells. The peptide stabilizes the MHC complex and interacts directly with the NK inhibitory receptors, thus participating in the determination of the fate of the target cells. In this study we demonstrate that posttranslational modifications such as phosphorylation of the presented peptide altered the ability of NK cells to recognize MHC class I molecules. By using a consensus peptide (QYDDAVYKL) that binds HLA-Cw4 in which different positions in the bound peptide were modified by serine phosphorylation, we observed a reduction in KIR2DL1 binding that led to decreased protection from NK killing. Therefore, it might be possible that alteration in the phosphorylation pattern during tumor transformation or viral infection may result in less inhibition and, consequently, improved NK cell killing.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Gili
authors.initials: G
authors.lastname: Betser-Cohen
authors.forename: Gil
authors.initials: G
authors.lastname: Katz
authors.forename: Tsufit
authors.initials: T
authors.lastname: Gonen-Gross
authors.forename: Noam
authors.initials: N
authors.lastname: Stern
authors.forename: Tal I
authors.initials: TI
authors.lastname: Arnon
authors.forename: Hagit
authors.initials: H
authors.lastname: Achdout
authors.forename: Roi
authors.initials: R
authors.lastname: Gazit
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000143:Acids / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology*; D002461:Cell Line, Transformed; D003601:Cytotoxicity Tests, Immunologic; D015236:HLA-C Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D055629:Natural Cytotoxicity Triggering Receptor 2; D009842:Oligopeptides / Q000276:immunology* / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000276:immunology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054342:Receptors, KIR2DL1; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D000143:Acids; D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; C039966:HLA-C*04 antigen; D007074:Immunoglobulin G; D008024:Ligands; C112837:NCR2 protein, human; D055629:Natural Cytotoxicity Triggering Receptor 2; D009842:Oligopeptides; D011971:Receptors, Immunologic; D054342:Receptors, KIR2DL1; D011993:Recombinant Fusion Proteins