Computational modeling of human natural killer cell development suggests a selection process regulating coexpression of KIR with CD94/NKG2A

Mali Salmon-Divon, Petter Höglund, Maria H. Johansson, Sofia Johansson, Ramit Mehr

Research output: Contribution to journalShort surveypeer-review

9 Scopus citations

Abstract

Natural killer cells fail to lyse target cells expressing sufficient levels of self MHC class I molecules, providing one mechanism to secure self tolerance. Inhibition of lysis is mediated by inhibitory receptors expressed by NK cells, such as the murine Ly49 receptors, human KIR receptors and CD94/NKG2A, expressed by both species. To ensure that most, if not all, NK cells express at least one inhibitory receptor for self MHC class I, selection processes have been postulated for murine NK cells regulating the number and identity of inhibitory receptors expressed by each cell. The presence of similar selection processes in human NK cells has not been demonstrated. In previous studies using mathematical modeling we have shown that, in the Ly49 system, the sequential model (in which gene expression and selection operate simultaneously) is most likely to explain the observed expression frequencies. We also predicted the parameters (such as receptor-ligand binding affinity levels) under which the models fit with the observed frequencies. This study aims to evaluate whether these models may be valid in the human system. Our data suggest that if selection operates during human NK cell development, it affects the co-expression of CD94/NKG2A and KIR rather than KIR expression alone, and is more likely to be governed by the two-step selection model.

Original languageEnglish
Pages (from-to)397-403
Number of pages7
JournalMolecular Immunology
Volume42
Issue number4 SPEC. ISS.
DOIs
StatePublished - Feb 2005

Bibliographical note

Funding Information:
This study was supported by grants from the Human Frontiers Science Foundation, and an Israel Science Foundation grant number 759/01-1 (to R.M.). The work was conducted partly in Bar-Ilan University, Israel, where it was part of a study performed towards a PhD degree, and partly within The Strategic Research Center for Immunoregulation (IRIS), funded by the Swedish Foundation for Strategic Research.

Keywords

  • Computer simulations
  • KIR
  • Ly49
  • Mathematical modeling
  • Natural killer cell development

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