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	Targeting naturally occurring epitope variants of hepatitis c virus with high-affinity t-cell receptors
	Zhang, Huajun1,3; Zhang, Jianbing2; Chen, Lei2; Weng, Zhiming2; Tian, Ye1; Zhao, Haifeng2; Li, Youjia1; Chen, Lin1; Liang, Zhaoduan1; Zheng, Hongjun2
刊名	Journal of general virology
	2017-03-01
卷号	98期号:3页码:374-384
关键词	Epitope mutation T cell exhaustion Phla Cytotoxic killing Anti-cd3
ISSN号	0022-1317
DOI	10.1099/jgv.0.000656
通讯作者	Li, yi(li_yi@gibh.ac.cn)
英文摘要	Hepatitis c virus (hcv) readily establishes chronic infection, which is characterized by failure of virus-specific cd8(+) t cells. hcv uses epitope mutation and t-cell exhaustion to escape from the host immune response. previously, we engineered high-affinity t-cell receptors (hats) targeting human immunodeficiency virus escape mutants. in this study, the affinity of a t-cell receptor specific for the hla-a2-restricted hcv immunodominant epitope ns3 1406-1415 (klvalginav) was improved from a k-d of 6.6 mu m to 40 pm. these hats could also target hcv ns3 naturally occurring variants, including an escape variant vrt1 (klvvlginav), with high affinities. the hats can be used as high-affinity targeting molecules at the centre of the immune synapse for the hla-restricted ns3 antigen. by fusing the hat with a t-cell activation molecule, an anti-cd3 single-chain variable fragment, we constructed a molecule called high-affinity t-cell activation core (hatac), which can redirect functional ctls possessing any specificity to recognize and kill cells presenting hcv ns3 antigens. this capability was verified with t2 cells loaded with prototype or variant peptides and hepg2 cells expressing the truncated ns3 prototype or variant proteins. the results indicate that hatac targeting the hla-restricted ns3 antigen may provide a useful tool for circumventing immune escape mutants and t-cell exhaustion caused by hcv infection.
WOS关键词	PREEXISTING VARIANTS ; IMMUNE ESCAPE ; INFECTION ; THERAPY ; HCV ; TRANSPLANTATION ; RESPONSES ; CD8 ; CRYSTALLIZATION ; IDENTIFICATION
WOS研究方向	Biotechnology & Applied Microbiology ; Virology
WOS类目	Biotechnology & Applied Microbiology ; Virology
语种	英语
出版者	MICROBIOLOGY SOC
WOS记录号	WOS:000399235600009
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2373446
专题	武汉病毒研究所
通讯作者	Li, Yi
作者单位	1.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China 2.XiangXue Pharmaceut Co Ltd, XiangXue Life Sci Res Ctr, Guangzhou, Guangdong, Peoples R China 3.Chinese Acad Sci, Wuhan Inst Virol, Wuhan, PR, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Huajun,Zhang, Jianbing,Chen, Lei,et al. Targeting naturally occurring epitope variants of hepatitis c virus with high-affinity t-cell receptors[J]. Journal of general virology,2017,98(3):374-384.
APA	Zhang, Huajun.,Zhang, Jianbing.,Chen, Lei.,Weng, Zhiming.,Tian, Ye.,...&Li, Yi.(2017).Targeting naturally occurring epitope variants of hepatitis c virus with high-affinity t-cell receptors.Journal of general virology,98(3),374-384.
MLA	Zhang, Huajun,et al."Targeting naturally occurring epitope variants of hepatitis c virus with high-affinity t-cell receptors".Journal of general virology 98.3(2017):374-384.

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