HLA-G is found in lipid rafts and can act as a signaling molecule.
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.
Comiskey
Martina
M
Department of Biology, Northeastern University, Boston, MA 02115, USA.
Domino
Kenneth E
KE
Warner
Carol M
CM
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006680:HLA Antigens / Q000235:genetics / Q000502:physiology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D021962:Membrane Microdomains / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D017252:CD3 Complex; C485468:Cd3e protein, mouse; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I