HLA-G is found in lipid rafts and can act as a signaling molecule

Hum Immunol. 2007 Jan;68(1):1-11. doi: 10.1016/j.humimm.2006.09.005. Epub 2006 Nov 3.


HLA-G protein is the functional homolog of Qa-2, the product of the mouse preimplantation embryo development (Ped) gene. Embryos expressing Qa-2 on the cell surface exhibit a faster rate of preimplantation cleavage and preferential survival in utero compared with Qa-2-negative embryos. Qa-2 is glycosylphosphatidylinositol (GPI) linked in the cell membrane. As a result, Qa-2 proteins cluster in cholesterol- and sphingolipid-rich lipid raft microdomains in the cell membrane and can signal via raft-associated intracellular signaling molecules. Using T cells as a model system, cross-linking of Qa-2 on the cell membrane has been shown to induce proliferation of resting cells. HLA-G, like Qa-2, lacks a cytoplasmic domain capable of transducing signals from the cell surface to the nucleus, but unlike Qa-2, HLA-G has a short six-amino acid cytoplasmic tail rather than a GPI anchor. To test whether HLA-G, like Qa-2, is located in lipid rafts and can act as a signaling molecule, we used an HLA-G transgenic mouse system. T cells were isolated and tested for HLA-G expression by immunofluorescence and for localization of HLA-G in lipid rafts by immunofluorescence and Western blotting. Next, the T cells were cross-linked with anti-HLA-G antibody to test for induction of proliferation. Our novel results show that HLA-G, like GPI-linked Qa-2, is present in lipid rafts in the cell membrane and can act as a signaling molecule to induce proliferation of resting T cells.

Publication types

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

MeSH terms

  • Animals
  • CD3 Complex / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • HLA Antigens / genetics
  • HLA Antigens / physiology*
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / physiology*
  • Humans
  • Lymphocyte Activation / genetics
  • Membrane Microdomains / genetics
  • Membrane Microdomains / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology


  • CD3 Complex
  • Cd3e protein, mouse
  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I