Implications of CD94 deficiency and monoallelic NKG2A expression for natural killer cell development and repertoire formation

Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):868-73. doi: 10.1073/pnas.022500599. Epub 2002 Jan 8.

Abstract

Natural killer (NK) cells are believed to achieve self-tolerance through the expression of self-MHC-specific inhibitory receptors, such as members of the Ly49 and CD94/NKG2 families. Individual Ly49 genes are stochastically expressed by NK subsets and are expressed in a monoallelic fashion, but little is known about the mechanisms underlying CD94/NKG2A expression. We show here that, like Ly49 genes, mouse Nkg2a is stochastically and monoallelically expressed. Thus, a single general mechanism controls expression of all known MHC-specific receptors by mouse NK cells. In addition, we find that DBA/2J mice are naturally CD94-deficient and do not express cell-surface CD94/NKG2A receptors, even on neonatal NK cells. Thus, self-tolerance of neonatal NK cells cannot be attributed to CD94/NKG2A expression. Taken together, the results lead to a reconsideration of current models of NK cell development and self-tolerance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Animals, Newborn
  • Antibodies, Monoclonal
  • Antibody Specificity
  • Antigens, CD / genetics
  • Antigens, Ly*
  • Cell Differentiation
  • Gene Expression
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type*
  • Membrane Glycoproteins / deficiency*
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Models, Immunological
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Receptors, Immunologic / genetics*
  • Receptors, NK Cell Lectin-Like
  • Receptors, Natural Killer Cell
  • Self Tolerance
  • T-Lymphocyte Subsets / immunology
  • Thymus Gland / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Ly
  • Klrc1 protein, mouse
  • Klrd1 protein, mouse
  • Lectins, C-Type
  • Membrane Glycoproteins
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Receptors, Immunologic
  • Receptors, NK Cell Lectin-Like
  • Receptors, Natural Killer Cell