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Related Experiment Videos

Killer cell receptors: keeping pace with MHC class I evolution

N M Valiante1, K Lienert, H G Shilling

  • 1Department of Structural Biology, Stanford University, School of Medicine, CA 94305-5400, USA.

Immunological Reviews
|February 1, 1997
PubMed
Summary

Natural killer (NK) cells use killer cell inhibitory receptors (KIRs) to recognize MHC class I molecules. This interaction shapes NK cell development and drives evolution of immune system diversity.

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Area of Science:

  • Immunology
  • Evolutionary Biology
  • Genetics

Background:

  • Natural killer (NK) cells possess receptors that bind to variable regions of MHC class I heavy chains.
  • MHC ligands exhibit significant diversity across mammalian species.
  • Distinct NK cell receptor families in humans and mice suggest rapid co-evolution.

Purpose of the Study:

  • To investigate the evolutionary dynamics of NK cell receptors and their MHC class I ligands.
  • To understand the relationship between killer cell inhibitory receptors (KIRs) and MHC class I recognition in primates.
  • To explore the implications of NK cell receptor-MHC interactions for immune repertoire development and evolutionary selection.

Main Methods:

  • Comparative analysis of NK cell receptor families (KIRs, C-type lectins) across species.

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  • Examination of the co-evolutionary patterns between NK cell receptors and MHC class I molecules.
  • Assessment of NK cell receptor expression and ligand availability in individual humans.

    • Main Results:

    • KIRs, found in primates, recognize MHC class I epitopes of recent evolutionary origin, suggesting a more recent evolution of KIR function compared to C-type lectins.
    • Individual humans may express NK cell receptors lacking corresponding MHC class I ligands.
    • A single donor study indicated that all NK cells express at least one inhibitory receptor for a self-HLA class I allotype, supporting the 'missing self' hypothesis.

    Conclusions:

    • The NK cell receptor-MHC class I interaction is crucial for controlling the NK cell repertoire during an individual's development.
    • This interaction acts as a selective force, influencing the diversity of both MHC class I and NK cell receptors throughout species evolution.