International Immunology Advance Access originally published online on June 10, 2008
International Immunology 2008 20(8):981-991; doi:10.1093/intimm/dxn057
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Four novel ULBP splice variants are ligands for human NKG2D
1 Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, National Key Laboratory of Medical Molecular Biology, 5 Dong Dan San Tiao, Beijing 100005, China
2 Department of Neurology, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Peking Union Hospital, Beijing, China
Correspondence to: W. He; E-mail: heweiimu{at}public.bta.net.cn
UL16-binding proteins [ULBPs, also termed as retinoic acid early transcripts (RAET1) molecules] are frequently expressed by malignant transformed cells and stimulate anti-tumor immune responses mediated by NKG2D-positive NK cells, CD8+ 
β T cells and 
T cells in vitro and in vivo. In this study, we identified four novel functional splice variants of ULBPs including ULBP4-I, ULBP4-II, ULBP4-III and RAET1G3 in HepG2 liver carcinoma cells, WISH human amnion cells, Hep-2 larynx carcinoma cells and K562 leukemia cells, respectively, by reverse transcription–PCR and T vector cloning strategy. Analysis of alignments of amino acid sequences of the splice variants illustrated that there were important modifications between splice variants and their individual parental ULBP. All ULBP4 splice variants (ULBP4-I, ULBP4-II and ULBP4-III) were type 1 membrane-spanning molecules and had the ability to bind with human NKG2D receptor in vitro. Ectopic expressions of ULBP4 and ULBP4 splice variants resulted in the enhanced cytotoxic sensitivity of target cells against NK cells, which could be blocked by anti-NKG2D mAb. Moreover, co-culture-free soluble forms of ULBP4 splice variants (their 1 + 2 ectodomains) and RAET1G3 (soluble splice variant of RAET1G2) with NK cells down-regulated the cell surface expression of NKG2D. Finally, immobilized in a plate-bound form of RAET1G3 stimulated NK cells to secrete IFN-. Taken together, all the identified functional splice variants will help to advance our knowledge regarding the overall functions of ULBP gene family.
Keywords: MHC-I like molecules, NK cells, splice variants, tumor immunity
* These authors contributed equally to this work.
Received 21 December 2007, accepted 14 May 2008.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Kong, W. Cao, X. Xi, C. Ma, L. Cui, and W. He The NKG2D ligand ULBP4 binds to TCR{gamma}9/{delta}2 and induces cytotoxicity to tumor cells through both TCR{gamma}{delta} and NKG2D Blood, July 9, 2009; 114(2): 310 - 317. [Abstract] [Full Text] [PDF]
|
|