Submitted December 22, 2008
Accepted April 23, 2009
The NKG2D ligand ULBP4 binds to TCR
9/
2 and induces cytotoxicity to tumor cells through both TCR and NKG2D
Yan Kong, Wei Cao, Xueyan Xi, Chi Ma, Lianxian Cui, and Wei He*
Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China
* Corresponding author; email: heweiimu{at}public.bta.net.cn.
UL16 binding proteins (ULBPs) belong to a family of ligands for NKG2D activating receptor of human NK cells. We previously reported that RAET1E2, a soluble isoform of the RAET1E (ULBP4) inhibits NKG2D-mediated NK cytotoxicity. In this study we examined whether ULBP4 could be recognized by 
T cells via TCR. Here we show that immobilized soluble ULBP4 (rULBP4) induces the proliferation of human ovarian epithelial carcinoma- or colonic carcinoma-derived V2+ T cells in vitro. These V2+ T cells secrete Th1 cytokines and display a strong cytolytic activity towards ULBP4 transfected targets. We also show that ULBP4 binds to a soluble chimeric protein containing TCR9/2 and activate TCR- Jurkat T cells transfected with TCR9/2. Moreover, both TCR and NKG2D are involved in ULBP4-induced activation and cytotoxicity of T cells. We found that ULBP4 is expressed not only on human tumor cells, but also on EBV infected peripheral blood cells. Taken together, our data suggest that ULBP4 functions as a ligand for both TCR and NKG2D and may play a key role in immune surveillance of tumor development and clearance of viral infection.
