Reduced KIR2DL1 recognition of MHC class I molecules presenting phosphorylated peptides

Gili Betser-Cohen, Gil Katz, Tsufit Gonen-Gross, Noam Stern, Tal I. Arnon, Hagit Achdout, Roi Gazit, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageAmerican English
Pages (from-to)6762-6769
Number of pages8
JournalJournal of Immunology
Issue number11
StatePublished - 1 Jun 2006


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