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Related Experiment Videos

Major histocompatibility complex genes determine natural killer cell tolerance

J R Dorfman1, D H Raulet

  • 1Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.

European Journal of Immunology
|January 1, 1996
PubMed
Summary

Murine natural killer (NK) cells show self-tolerance through mechanisms distinct from Ly49A or Ly49C receptors. This involves inhibition mediated by beta 2-microglobulin-dependent MHC class I molecules, not anergy.

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Area of Science:

  • Immunology
  • Cellular immunology
  • NK cell biology

Background:

  • Murine natural killer (NK) cells express Ly49 receptors that recognize major histocompatibility complex (MHC) class I alleles.
  • Ly49A+ NK cells can distinguish between different MHC class I alleles, such as H-2b and H-2d, on target cells.
  • The mechanism of NK cell self-tolerance, particularly in the context of recognizing self-MHC, remains an important question.

Purpose of the Study:

  • To investigate the mechanisms underlying self-tolerance in Ly49A+ NK cells.
  • To determine if NK cell tolerance is mediated by anergy or inhibitory receptor signaling.
  • To identify the specific inhibitory receptors involved in self-MHC recognition by NK cells.

Main Methods:

  • Comparison of lysis of H-2b (self) and H-2d target cells by IL-2-cultured Ly49A+ effector cells from H-2b and H-2d mice.

Related Experiment Videos

  • Assessment of beta 2-microglobulin-deficient target cells to evaluate anergy.
  • Functional blockade of Ly49A and Ly49C receptors on effector NK cells.

    • Main Results:

    • Ly49A+ effector cells from H-2b mice showed reduced lysis of H-2b target cells compared to H-2d target cells, indicating self-tolerance.
    • Tolerance was not due to anergy, as beta 2-microglobulin-deficient target cells were lysed equivalently.
    • Inhibition of H-2b target cell lysis was not mediated by Ly49A or Ly49C receptors, suggesting involvement of other inhibitory receptors.

    Conclusions:

    • Self-tolerance in Ly49A+ NK cells from H-2b mice is mediated by inhibitory receptors distinct from Ly49A and Ly49C.
    • This tolerance involves beta 2-microglobulin-dependent MHC class I molecules.
    • NK cells possess mechanisms to avoid auto-reactivity against self-MHC molecules.