Cutting edge: expression of functional CD94/NKG2A inhibitory receptors on fetal NK1.1+Ly-49- cells: a possible mechanism of tolerance during NK cell development

J Immunol. 1999 Jun 15;162(12):6976-80.

Abstract

Fetal liver- and thymus-derived NK1.1+ cells do not express known Ly-49 receptors. Despite the absence of Ly-49 inhibitory receptors, fetal and neonatal NK1.1+Ly-49- cells can distinguish between class Ihigh and class Ilow target cells, suggesting the existence of other class I-specific inhibitory receptors. We demonstrate that fetal NK1. 1+Ly-49- cell lysates contain CD94 protein and that a significant proportion of fetal NK cells are bound by Qa1b tetramers. Fetal and adult NK cells efficiently lyse lymphoblasts from Kb-/-Db-/- mice. Qa1b-specific peptides Qdm and HLA-CW4 leader peptide specifically inhibited the lysis of these blasts by adult and fetal NK cells. Qdm peptide also inhibited the lysis of Qa1b-transfected human 721.221 cells by fetal NK cells. Taken together, these results suggest that the CD94/NKG2A receptor complex is the major known inhibitory receptor for class I (Qa1b) molecules on developing fetal NK cells.

Publication types

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

MeSH terms

  • Aging / immunology
  • Amino Acid Sequence
  • Animals
  • Antigens / biosynthesis*
  • Antigens, CD / biosynthesis*
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, Ly*
  • Antigens, Surface
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell-Free System / immunology
  • Cells, Cultured
  • Cytotoxicity, Immunologic / drug effects
  • Cytotoxicity, Immunologic / genetics
  • Fetus
  • Histocompatibility Antigens Class I / biosynthesis
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Immune Sera / chemistry
  • Immune Tolerance* / genetics
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Lectins, C-Type*
  • Liver / cytology
  • Liver / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / genetics
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • NK Cell Lectin-Like Receptor Subfamily B
  • NK Cell Lectin-Like Receptor Subfamily D
  • Peptides / immunology
  • Peptides / pharmacology
  • Protein Binding / immunology
  • Protein Biosynthesis*
  • Proteins*
  • Receptors, NK Cell Lectin-Like
  • Spleen / cytology
  • Spleen / growth & development
  • Spleen / immunology
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Transcription, Genetic / immunology
  • Transfection / immunology
  • Tumor Cells, Cultured

Substances

  • Antigens
  • Antigens, CD
  • Antigens, Ly
  • Antigens, Surface
  • Histocompatibility Antigens Class I
  • Immune Sera
  • KLRB1 protein, human
  • Klrb1c protein, mouse
  • Klrd1 protein, mouse
  • Lectins, C-Type
  • Membrane Glycoproteins
  • NK Cell Lectin-Like Receptor Subfamily B
  • NK Cell Lectin-Like Receptor Subfamily D
  • Peptides
  • Proteins
  • Q surface antigens
  • Receptors, NK Cell Lectin-Like