Comparative analysis of NK-cell receptor expression and function across primate species: Perspective on antiviral defenses

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Natural killer (NK) cells are lymphoid effectors that are involved in the innate immune surveillance against infected and/or tumor cells. Their function is under the fine-tuning control of cell surface receptors that display either inhibitory or activating function and in healthy condition, mediate self-tolerance. It is known that inhibitory receptors are characterized by clonal and stochastic distribution and are extremely sensible to any modification, downregulation or loss of MHC class I surface expression that are induced in autologous cells upon viral infection or cancer transformation. This alteration of the MHC class I expression weakens the strength of the inhibitory receptor-induced interaction, thus resulting in a prompt triggering of NK cell function, which ends up in the inhibition of tumor progression and proliferation of pathogen-infected cells. Thus, the inhibitory function of NK cells is only one face of the coin, since NK-cell activation is controlled by different arrays of activating receptors that finally are involved in the induction of cytolysis and/or cytokine release. Interestingly, the inhibitory NK-cell receptors that are involved in dampening NK cell-mediated responses evolved during speciation in different, often structurally unrelated surface-expressed molecules, all using a conserved signaling pathway. In detail, during evolution, the inhibitory receptors that assure the recognition of MHC class I molecules, originate in, at least, three different ways. This ended up in multigene families showing marked structural divergences that coevolved in a convergent way with the availability of appropriate MHC ligand molecules.

Original languageEnglish
Pages (from-to)103-113
Number of pages11
JournalSelf/Nonself - Immune Recognition and Signaling
Issue number2
Publication statusPublished - Apr 2010


  • Gene loci evolution
  • Killer inhibitory receptor
  • Natural cytotoxicity receptors
  • NKG2D
  • Primate

ASJC Scopus subject areas

  • Immunology and Microbiology (miscellaneous)
  • Immunology


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