REGULAR ARTICLES

Cell research (2004); 14(2):155-160

Inhibition of the activating signals in NK92 cells by recombinant GST-sHLA-G1α chain

Ai Yu YAO^1,2, Hai Yang TANG¹, Yun WANG¹, Mei Fu FENG^1,*,　 Rou Li ZHOU^2,*

¹Staate Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Science, Beijing 100080, China.
²Department of Cell Biology and Medical Genetics, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100083, China.

Received, April 4, 2003    Revised, Mar 21, 2004    Accepted, Mar 25, 2004

Correspondence: Mei Fu FENG +86 10 62571017 (phone) +86 10 62571017 (fax) fengmf@panda.ioz.ac.cn and Rou Li ZHOU 408-731-5069 (phone) 408-732-7025 (fax) rlzhou@bjmu.edu.cn

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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-G1α  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-G1α  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 β-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.

Keywords: NK92, GST-sHLA-G1α  chain, signal transduction, SHP-1, O-GlcNAc.