The ILT2(LIR1) and CD94/NKG2A NK cell receptors respectively recognize HLA-G1 and HLA-E molecules co-expressed on target cells

Eur J Immunol. 1999 Jan;29(1):277-83. doi: 10.1002/(SICI)1521-4141(199901)29:01<277::AID-IMMU277>3.0.CO;2-4.

Abstract

Previous studies on NK recognition of HLA-G1 employed as targets 721.221 transfectants (.221-G1) that unknowingly co-expressed the HLA-E molecule, subsequently found to be a major ligand for the CD94/NKG2 receptors. In the present study we re-evaluated the relative role played by CD94/NKG2 and ILT2(LIR1) molecules in recognition of HLA-G1 by NK clones. We employed as targets .221-G1 cells and a surface HLA-E-negative transfectant, .221-G1(Eneg), generated by site-directed mutagenesis of the HLA-G1 leader sequence. The antagonistic effects of receptor- (ie. CD94/NKG2A, ILT2) and ligand-specific mAb (i.e. HLA-G, HLA-E) were assessed. In addition, binding of an ILT2-Ig fusion protein to the .221-AEH, expressing only HLA-E, and the .221-G1(Eneg) transfectants was analyzed. Our data demonstrate that NK recognition of cells expressing HLA-G1 involves at least two non-overlapping receptor-ligand systems: the CD94/NKG2 interaction with HLA-E, and the engagement of the ILT2(LIR1) receptor by HLA-G1 molecules.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal
  • Antigens, CD / metabolism*
  • Cell Line
  • HLA Antigens / genetics
  • HLA Antigens / metabolism*
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type*
  • Leukocyte Immunoglobulin-like Receptor B1
  • Ligands
  • Membrane Glycoproteins / metabolism*
  • Mutagenesis, Site-Directed
  • NK Cell Lectin-Like Receptor Subfamily D
  • Receptors, Immunologic / metabolism*
  • Transfection

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • HLA Antigens
  • HLA-E antigen
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • KLRD1 protein, human
  • LILRB1 protein, human
  • Lectins, C-Type
  • Leukocyte Immunoglobulin-like Receptor B1
  • Ligands
  • Membrane Glycoproteins
  • NK Cell Lectin-Like Receptor Subfamily D
  • Receptors, Immunologic