PMID- 18295671 OWN - NLM STAT- MEDLINE DCOM- 20080403 LR - 20111117 IS - 0198-8859 (Print) IS - 0198-8859 (Linking) VI - 69 IP - 1 DP - 2008 Jan TI - Human leukocyte antigen-G1 inhibits natural killer cytotoxicity through blocking the activating signal transduction pathway and formation of activating immunologic synapse. PG - 16-23 LID - 10.1016/j.humimm.2007.11.005 [doi] AB - Nonclassical major histocompatibility complex (MHC) class I molecule human leukocyte antigen (HLA)-G is normally expressed on the placental cells, especially fetal endothelial cells and invasive cytotrophoblast cells at the maternal-fetal interface. This antigen meditates immune tolerance in pregnancy through interaction with immune cells including natural killer (NK) cells. In this study, we investigated the mechanisms underlying HLA-G1-mediated inhibition of NK cytotoxicity using HLA-G1-transfected K562 cells and NK92 cells. We found that inhibition of NK cytotoxicity by HLA-G1 was associated with decreased formation of NK-target cell conjugates and defective formation of immunologic synapse, as characterized by actin depolarization and perforin immobilization in nonactive NK cells. HLA-G1 engagement induced dephosphorylation of Vav by tyrosine phosphatase-1 (SHP-1), and thus blocked the Syk-->MEK/ERK activating signaling pathway in activating NK cells. These results indicate that HLA-G1 inhibits NK cytotoxicity by blocking activating signal transduction pathway, which is required for the formation of activating immunologic synapse. FAU - Yu, Yanrong AU - Yu Y AD - State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China. FAU - Wang, Yun AU - Wang Y FAU - Feng, Meifu AU - Feng M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071226 PL - United States TA - Hum Immunol JT - Human immunology JID - 8010936 RN - 0 (HLA Antigens) RN - 0 (HLA-G Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Proto-Oncogene Proteins c-vav) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6) SB - IM MH - Actin Cytoskeleton/ultrastructure MH - Cell Line MH - *Cytotoxicity, Immunologic MH - HLA Antigens/*metabolism MH - HLA-G Antigens MH - Histocompatibility Antigens Class I/*metabolism MH - Humans MH - K562 Cells MH - Killer Cells, Natural/enzymology/*immunology/ultrastructure MH - *MAP Kinase Signaling System MH - Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism MH - Proto-Oncogene Proteins c-vav/metabolism EDAT- 2008/02/26 09:00 MHDA- 2008/04/04 09:00 CRDT- 2008/02/26 09:00 PHST- 2007/08/10 00:00 [received] PHST- 2007/11/05 00:00 [revised] PHST- 2007/11/13 00:00 [accepted] PHST- 2008/02/26 09:00 [pubmed] PHST- 2008/04/04 09:00 [medline] PHST- 2008/02/26 09:00 [entrez] AID - S0198-8859(07)00469-7 [pii] AID - 10.1016/j.humimm.2007.11.005 [doi] PST - ppublish SO - Hum Immunol. 2008 Jan;69(1):16-23. doi: 10.1016/j.humimm.2007.11.005. Epub 2007 Dec 26.