Inhibition of the activating signals in NK92 cells by recombinant GST-sHLA-G1a chain.
The soluble HLA-G1 (sHLA-G1) isoform was found to be secreted by trophoblast cells at the materno-fetal interface, which suggests that it may act as an immunomodulator during pregnancy. In this paper, we reported that GST-sHLA-G1a chain could bind to its receptor ILT-2 on NK92 cells and then the latter recruited Src homology 2 domain-containing tyrosine phosphatase-1 (SHP-1), which consequently dephosphorylated some important protein tyrosine kinases and blocked the activation of downstream molecules such as MEK and ERK so that the cytotoxicity of natural killer (NK) cells was inhibited. These results indicated that GST-sHLA-G1a chain might be exploited in new immunotherapy strategies aiming at inducing immunotolerance during allograft, xenograft and autoimmune situations. In addition, we found that modification of O-linked b-N-acetylglucosamine (O-GlcNAc) was involved in NK cells' activating and inhibitory signals. This may provide a novel molecular target for inducing immunotolerance but needs further study.
Yao
Ai Yu
AY
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Science, Beijing 100080, China.
Tang
Hai Yang
HY
Wang
Yun
Y
Feng
Mei Fu
MF
Zhou
Rou Lin
RL
D000117:Acetylglucosamine / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D005982:Glutathione Transferase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008213:Lymphocyte Activation / Q000276:immunology; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D014327:Trophoblasts / Q000276:immunology / Q000378:metabolism; D018909:src Homology Domains
D015703:Antigens, CD; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases; D000117:Acetylglucosamine